There is an urgent need to identify effective therapies for COVID-19. The SARS-CoV-2 host factor protease TMPRSS2 is required for viral entry and thus an attractive target for therapeutic intervention. In mouse, knockout of tmprss2 led to protection against SARS-CoV-1 with no deleterious phenotypes, and in human populations genetic loss of TMPRSS2 does not appear to be selected against. Here, we mined publicly available gene expression data to identify several compounds that down-regulate TMPRSS2. Recognizing the need for immediately available treatment options, we focused on FDA-approved drugs. We found 20 independent studies that implicate estrogenic and androgenic compounds as transcriptional modulators of TMPRSS2, suggesting these classes of drugs may be promising therapeutic candidates for clinical testing and observational studies of COVID-19. We also note that expression of TMPRSS2 is highly variable and skewed in humans, with a minority of individuals having extremely high expression. Combined with literature showing that inhibition of TMPRSS2 protease activity reduces SARS-CoV-2 viral entry in human cells, our results raise the hypothesis that modulation of TMPRSS2 expression is a promising therapeutic avenue for COVID-19.

A recent manuscript (Zhou, P. et al. “A pneumonia outbreak associated with a new coronavirus of probable bat origin”, Nature 579, 270–273 (2020). https://doi.org/10.1038/s41586-020-2012-7) from Wuhan Institute of Virology claimed the identification of a bat coronavirus, RaTG13, which showed 96.2% genome homology with SARS-CoV-2. In this paper, we raise the puzzling observations surrounding the identification, characterization, unique genome features of this RaTG13 strain, as well as its 100% nucleotide identity in partial RdRp gene with another bat coronavirus strain BtCoV/4991. And the paper presented premature hypothesis of potential bat origin of SARS-CoV-2 while RaTG13 strain was not successfully isolated. We also present the concerns on the methodology, data quality and experiment procedures described in this paper. We call for the authors to provide additional data, to share related samples to be verified and further characterized by other scientists.

Malaysia implemented a movement control order (MCO) to curb the spread of the SARS-CoV-2 virus in March 2020. Despite healthcare services remaining operational, rising COVID-19 infections and MCO restrictions have forced healthcare professionals to seek a compromise between service capacity and standard operating procedure compliance. A cross-sectional survey was conducted among public and private sector doctors, dentists and pharmacists to determine how lockdown measures impacted healthcare services. Responses from 413 doctors, 193 dentists, and 163 pharmacists were analysed. Pharmacy services remained mostly unaffected throughout the MCO. In contrast, operational capacities for surgical and dental services were severely affected during the MCO. All service sectors reported restricting patients or accompanying individuals at the workplace, reductions in staffing capacity, and shortened patient contact time at various degrees. Many pharmacy and medical participants reported supplying extended medication supplies to patients. Adoption of virtual healthcare services was generally poor. All private service sectors suffered financial losses ranging between 59 to 75%. Periodic assessments of the healthcare system throughout the pandemic are required to identify which patients have their treatment compromised so that healthcare managers and policy makers can plan and implement appropriate interventions that help alleviate pressure within the health system.

As of 26 March 2020, Pakistan had 1179 cases of COVID-19, with most 421 cases from Sindh, 394 cases, 131 cases, 123 cases, 84 cases, 25 cases and 01 cases from Punjab, Balochistan, Khyber Pakhtunkhwa, Gilgit-Baltistan, Islamabad Capital Territory, and Azad Jammu and Kashmir respectively. Travel-related cases were the main source of SARS-CoV-2 infection during the early phase of the pandemic in Pakistan. Nevertheless, cases of local virus transmission are increasing day by day. As of 26 March 2020, nine deaths have been reported from COVID-19. The case fatality rate is 0.8%, which is less compare to China, Italy, USA, and Iran. The SIR (Susceptible-Infected-Recovered) model of epidemiological analysis predicts that almost 90 million population will be infected in the coming days with 5% critical cases that need health care facilities. However, the Pakistan health care system cannot provide services to this much population. Hence, we need to act timely to reduce this number by restricting local transmission of the disease. This can be done by mass testing, quarantine, isolation and social distancing of the active coronavirus cases in Pakistan. Moreover, better communication between the authorities is very much required to control disease transmission.

The COVID-19 pandemic is due to infection caused by the novel SARS-CoV-2 that impacts the lower respiratory tract. The spectrum of symptoms ranges from asymptomatic infections to mild respiratory symptoms to the lethal form of COVID-19 which is associated with severe pneumonia, acute respiratory distress and fatality. At present, the global case fatality rate of COVID-19 laboratory confirmed cases is ~4.7% ranging from ~0.3-0.4% in Chile and Israel to ~10.8% in Italy. To address this global crisis, up-to-date information on the viral genomics and transcriptomics is crucial for understanding the origins and global dispersal of the virus, providing insight into viral pathogenicity, transmission and epidemiology, and enabling strategies for therapeutic interventions, drug discovery and vaccine development. Therefore, this review provides a comprehensive overview of COVID-19 epidemiology, genomic etiology, findings from recent transcriptomic map analysis, viral-human protein interactions, molecular diagnostics, and the current status of vaccine and novel therapeutic intervention development. Moreover, we provide an extensive list of resources that will help the scientific community access numerous types of databases related to SARS-CoV-2 OMICs and approaches to therapeutics related to COVID-19 treatment.

SARS-CoV-2 is a novel coronavirus that is the causative agent of Coronavirus infectious disease 2019 (COVD-19). As of the 17^th April 2020, it has infected 2 114 269 people resulting in 145 144 deaths. The timing, magnitude and longevity of humoral immunity is not yet understood for SARS-CoV-2. Nevertheless, understanding this is urgently required to inform the likely future dynamics of the pandemic, to guide strategies to allow relaxation of social distancing measures and to understand how to deploy limiting vaccine doses when they become available to achieve maximum impact. SARS-CoV-2 is the seventh human coronavirus to be described. Four human coronaviruses circulate seasonally and cause common colds. Two other coronaviruses, SARS and MERS, have crossed from animal sources into humans but have not become endemic. Here we review what is known about the human humoral immune response to epidemic SARS CoV and MERS CoV and to the seasonal, endemic coronaviruses. Then we summarize recent, mostly non-peer reviewed studies into SARS-CoV-2 serology and reinfection in humans and non-human primates and summarize current pressing research needs.

Azithromycin has been shown to have a clinical efficacy against severe acute respiratory syndrome coronavirus 2 (SARS CoV-2); ivermectin has also demonstrated a remarkable experimental efficacy with a potential to be used for Coronavirus disease 2019 (COVID-19). Further, BCG vaccination is being considered for clinical trials aiming to test its potential for lowering COVID-19 morbidity and mortality. This article illustrates some structural and functional relationships that may gather these drugs and the author, basing on a combined pathophysiological and pharmacological approach, recommends the FDA-approved antidiarrhea drug; nitazoxanide, which has been previously suggested but unfortunately ignored, to be tested in combination with azithromycin for their potential activity against SARS CoV-2 soonest. The author recommends testing their combined administration as early during the clinical course of COVID-19 as possible. Further, basing on the same represented concept, the author recommends more trials for interferons to be tested against SARS CoV-2 especially in severe and critical cases.

COVID-19 (2019-nCoV) is a pandemic disease with an estimated mortality rate of 3.4% (estimated by the WHO as of March 3, 2020). Until now there is no antiviral drug and vaccine for COVID-19. The current overwhelming situation by COVID-19 patients in hospitals is likely to increase in the next few months. About 15 percent of patients with serious disease in COVID-19 require immediate health services. Rather than waiting for new anti-viral drugs or vaccines that take a few months to years to develop and test, several researchers and public health agencies are attempting to repurpose medicines that are already approved for another similar disease and have proved to be fairly effective. This study aims to identify FDA approved drugs that can be used for drug repurposing and identify biomarkers among high- risk and asymptomatic groups. In this study gene-disease association related to COVID-19 reported mild, severe symptoms and clinical outcomes were determined. The high-risk group was studied related to SARS-CoV-2 viral entry and life cycle by using Disgenet and compared with curated COVID-19 gene data sets from the CTD database. The overlapped gene sets were enriched and the selected genes were constructed for protein-protein interaction networks. Through interactome, key genes were identified for COVID-19 and also for high risk and asymptomatic groups. The key hub genes involved in COVID-19 were VEGFA, TNF, IL-6, CXCL8, IL10, CCL2, IL1B, TLR4, ICAM1, MMP9. The identified key genes were used for drug-gene interaction for drug repurposing. The chloroquine, lenalidomide, pentoxifylline, thalidome, sorafenib, pacitaxel, rapamycin, cortisol, statins were proposed to be probable drug repurposing candidates for the treatment of COVID-19. However, these predicted drug candidates need to be validated through randomized clinical trials. Also, a key gene involved in high risk and the asymptomatic group were identified, which can be used as probable biomarkers for early identification.

We review and assess the classic SIR and SEIR epidemiological models regarding possible applications to the COVID-19 pandemic. In spite of numerous more complicated models, we show how the qualitative features of the solution to the SIR and SEIR models continue to provide valuable public health insights in some scenarios. Using estimated COVID-19 data as of this date, the SEIR model shows that if it were possible to reduce R₀ from 2.5 to 1.25 through social distancing and other measures, the maximum fraction of the population that would become infected at any particular time would drop from 17% to 4%, provided that all of the model assumptions are satisfied. Finally, we compare the classic SIR model with a recent stochastic model with favorable results. Since this comparison underscores the importance of underlying connectivity assumptions, we conclude with Monte-Carlo simulations with specific connectivity that reproduce the classical SIR model with standard incidence.

Since the Coronavirus disease (COVID-19) outbreak at the end of 2019, the past two month has seen an acceleration both in and outside China in the R&D of the diagnostics, vaccines and therapeutics for this novel coronavirus. As one of the molecular forces that determine protein structure, electrostatic effects dominate many aspects of protein behaviour and biological function. Thus, incorporating currently available experimental structures related to COVID-19, this article reports a simple python-based analysis tool and a LaTeX-based editing tool to extract and summarize the electrostatic features from experimentally determined structures, to strengthen our understanding of COVID-19's structure and function and to facilitate machine-learning and structure-based computational design of its neutralizing antibodies and/or small molecule(s) as potential therapeutic candidates. Finally, this article puts forward a brief update of the structurally observed electrostatic features of the COVID-19 coronavirus.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes an outbreak of COVID-19 disease in humans with the aid of spike protein. It consists of a receptor-binding domain (RBD) that recognizes and binds to the host receptor angiotensin-converting enzyme 2 (ACE2). The aim of this study was to examine the mutational effect of spike protein on the sequence through an interaction study of the mutant spike protein and the human ACE2 protein at the structural level. A total of 17,227 spike proteins from Asia, Africa, Europe, Oceania, South America, and North America were compared to the Wuhan spike protein reference sequence (Wuhan-Hu-1). The structural and stability implications of D614G, N501Y, and S477N mutations were evaluated. The binding affinity between mutated RBD and human ACE2 protein was also studied. The D614G mutation may have originated in Germany, Europe based on the date of the first sample collection report. It is now widely circulated all over the world with most occurrences in North America. The mutations N501Y and S477N may have originated from Oceania based on the date of the first sample collection report and also have the highest occurrences in Oceania. Based on the computational analysis of mutational effects, the D614G, N501Y, and S477N mutations decreased stability and were tolerated. For disease propensity prediction, N501Y was more prone to disease compared to D614G, while S477N was not prone to disease. The mutation of D to G at position 614 and S to N at position 477 for secondary structure prediction shows no changes in secondary structure while remaining in the coil region, whereas the mutation of N to Y at position 501 changes from coil structure to extended strand. N501Y mutation has a higher affinity to human ACE2 protein compared to D614G and S477N based on a docking study. D614G spike mutation was identified to exist between the two hosts based on a comparison of SARS-CoV-2 derived between the mink and human. Further research is needed on the link between the mink mutation N501T and the mutation N501Y in humans, which has evolved as a separate variant.

After the appearance of first cases of ‘pneumonia of unknown origin’ in the Wuhan city, China, during late 2019, the disease progressed fast. Its cause was identified as a novel coronavirus, named provisionally 2019-nCoV. Subsequently, an official name was given as SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) by the International Committee on Taxonomy of Viruses (ICTV) study group. The World Health Organization (WHO) named the Coronavirus disease-2019 as COVID-19. The epidemics of COVID-2019 have been recorded over 113 countries/territories/areas apart from China and filched more than 4292 humans, affecting severely around 1,18,326 cases in a short span. The status of COVID-2019 emergency revised by the WHO within 42 days from Public Health International Emergency (January 30, 2020) to a pandemic (March 11, 2020). Nonetheless, the case fatality rate (CFR) of the current epidemic is on the rise (between 2-4%), relatively is lower than the previous SARS-CoV (2002/2003) and MERS-CoV (2012) outbreaks. Even though investigations are on its way, the researchers across the globe have assumptions of animal-origin of current SARS-CoV-2. A recent case report provides evidence of mild COVID-2019 infection in a pet dog that acquired COVID-2019 infection from his owner in Hong Kong. The news on travellers associated spread across the globe have also put many countries on alert with the cancellation of tourist visa to all affected countries and postponement of events where international visits were required. A few diagnostic approaches, including quantitative and differential real-time polymerase chain reaction assays, have been recommended for the screening of the individuals at risk. In the absence of any selective vaccine against SARS-CoV-2, re-purposed drugs are advocated in many studies. This article discourse the current worldwide situation of COVID-2019 with information on virus, epidemiology, host, the role of animals, effective diagnosis, therapeutics, preventive and control approaches making people aware on the disease outcomes.

The recent pandemic has greatly stressed supply chains, treatment modalities, and medical resources. Cold atmospheric plasma (CAP) has been used for a wide range of applications in biomedical engineering due to its many components including electrons, charged particles, reactive oxygen species (ROS), reactive nitrogen species (RNS), free radicals, ultraviolet (UV) photons, molecules, electromagnetic fields, physical forces, and electric fields. In this manuscript, we develop CAP devices for COVID-19. Our manuscript indicates the advantages of highlydeployable CAP devices for both sanitation and treatment, without the need for supply chains of special consumables such as hand sanitizers and the like. We hope that this timely research will help engage the broader community of engineers that wish to help the medical community with this pandemic and to prevent and treat future outbreaks.

RLF-100 (Aviptadil), a synthetic form of Vasoactive Intestinal Peptide (VIP) is shown to block replication of the SARS-CoV-2 virus and has been granted Fast Track Designation by the US FDA for the treatment of Critical COVID-19 with Respiratory Failure. We describe the clinical course of the first patient treated with this investigational medication in an open label manner -- a 54 year old patient suffering antibody-mediated rejection of his double lung transplant who contracted COVID-19 with respiratory failure refractory to all currently available therapies. He received three infusions of RLF-100 under an FDA-approved emergency use IND. Within 24 hours of the third infusion, substantial improvement in oxygen saturation and radiographic improvement in characteristic COVID-19 pneumonitis was noted. He was discharged from intensive care at that point and scheduled for discharge to home at 1 week on room air. Despite an intervening hospitalization for trauma, he remains alive and free of respiratory failure at 28 days post treatment.

Background. The main impetus behind the worldwide Covid-19 vaccination campaign in 2021 was to reduce the mortality attributed to SARS-CoV-2 infection in the preceding year. Nevertheless, rigorous analyses of the mortality benefits conferred by this massive vaccination effort have been lacking. Methods Statistics offers us an essential methodological approach for measuring the impacts of Covid-19 vaccination on public health. The mathematical relation between vaccinated-alive groups can be repeated between vaccinated-dead groups with relatively high statistical reliability because of the large population numbers involved. This method also confers greater statistical usefulness because it eliminates the Simpson effect. Results Calculations were performed for each of the following five(5) four-week intervals: weeks 35-38 (2021), weeks 39-42 (2021), weeks 43-46 (2021), weeks 47-50 (2021), and weeks 50(2021)-1(2022). The results obtained confirm that the mortality of the vaccinated coronavirus-infected groups was 14.5% higher on average than the mortality of non-vaccinated coronavirus-infected groups. Conclusions Vaccinated infected groups appear to have higher average mortality than their non-vaccinated infected counterparts. The findings suggest the legitimacy of extending the statistics between vaccinated living and vaccinated dead individuals for different age groups. Calculating the impact of Covid-19 vaccination on the mortality rate is a necessary step towards satisfying the first principle of medicine: “Primum non nocere”, “Do no harm”.

The global pandemic of SARS-CoV-2, the causative viral pathogen of COVID-19, has driven the biomedical community to action – to uncover and develop anti-viral interventions. One potential therapeutic approach currently being evaluated in numerous clinical trials is the agent remdesivir, which has endured a long and winding developmental path. Remdesivir is a nucleotide analog prodrug that perturbs viral replication, originally evaluated in clinical trials to thwart the Ebola outbreak in 2014. Subsequent evaluation by numerous virology laboratories demonstrated the ability of remdesivir to inhibit coronavirus replication, including SARS-CoV-2. Here, we provide an overview of its mechanism of action, discovery, and the current studies exploring its clinical effectiveness.

Background: Coronavirus disease 2019 (COVID-19) pandemic are causing significant damages to many nations. For mitigating its risk, Japan’s Prime Minister called on all elementary, junior high and high schools nationwide to close beginning March 1, 2020. However, its effectiveness in decreasing disease burden has not been investigated. Methods: We used daily data on the report of COVID-19 and coronavirus infection incidence in Japan until March 31, 2020. Time series analysis were conducted using Bayesian method. Local linear trend models with interventional effect were constructed for number of newly reported cases of COVID-19, including asymptomatic infections. We considered that the effects of intervention start to appear 9 days after the school closure; i.e., on March 9. Results: The intervention of school closure did not appear to decrease the incidence of coronavirus infection. If the effectiveness of school closure began on March 9, mean coefficient α for effectiveness of the measure was calculated to be 0.08 (95% credible interval -0.36 to 0.65), and the actual reported cases were more than predicted, yet with rather wide credible interval. Sensitivity analyses using different dates also showed similar results. Conclusions: School closure carried out in Japan did not show the effectiveness to mitigate the transmission of novel coronavirus infection.

Background: Countries around the world are facing extraordinary challenges in implementing various measures to slow down the spread of the novel coronavirus (COVID-19). Guided by international recommendations, Saudi Arabia has implemented a series of infection control measures after the detection of the first confirmed case in the country. However, in order for these measures to be effective, public attitudes and compliance must be conducive as perceived risk is strongly associated with health behaviors. The primary objective of this study is to assess Saudis’ attitudes towards COVID-19 preventive measures to guide future health communication content. Methods: Naïve Bayes machine learning model was used to run Arabic sentiment analysis of Twitter posts through the Natural Language Toolkit (NLTK) library in Python. Tweets containing hashtags pertaining to seven public health measures imposed by the government were collected and analyzed. Results: A total of 53,127 tweets were analyzed. All measures, except one, showed more positive tweets than negative. Measures that pertain to religious practices showed the most positive sentiment. Discussion: Saudi Twitter users showed support and positive attitudes towards the infection control measures to combat COVID-19. It is postulated that this conducive public response is reflective of the overarching, longstanding popular confidence in the government. Religious notions may also play a positive role in preparing believers at times of crises. Findings of this study broadened our understanding to develop proper public health messages and promote stronger compliance with control measures to control COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is pandemic. Prevention and control strategies require an improved understanding of SARS-CoV-2 dynamics. We did a rapid review of the literature on SARS-CoV-2 viral dynamics with a focus on infective dose. We sought comparisons of SARS-CoV-2 with other respiratory viruses including SARS-CoV-1 and MERS-CoV. We examined laboratory animal, and human studies. The literature on infective dose, transmission, and routes of exposure was limited specially in humans, and varying endpoints were used for measurement of infection. We propose the minimum infective dose of COVID-19 in humans, is higher than 100 particles, possibly slightly lower than the 700 particles estimated for H1N1 influenza. Despite variability in animal studies, there was some evidence that increased dose at exposure correlated with higher viral load clinically, and severer symptoms. Higher viral load measures did not reflect COVID-19 severity. Aerosol transmission seemed to raise the risk of more severe respiratory complications in animals. An accurate quantitative estimate of the infective dose of SARS-CoV-2 in humans is not currently feasible and needs further research. Further work is also required on the relationship between routes of transmission, infective dose, co-infection, and outcomes.

The greatest pandemic of the century, COVID-19, is an ongoing global public health problem. With a clinically approved treatment available only for those who are acutely ill and are hospitalized, the control of this disease in the general population is still largely dependent on the preventive measures issued by the World Health Organization. Among the general control measures other than immunization with the COVID-19 vaccines, handwashing with soap and water has been emphasized the most because it is cost-effective and easily accessible to the general public. Studies have reported that soaps offer unique chemical properties that can completely destroy enveloped viruses. However, the general public seems to be still uncertain about whether soaps can shield us from a highly contagious disease such as COVID-19. In an attempt to help eliminate the uncertainty, we analyzed the mechanisms underlying the efficacy of soap and its prospect for preventing the spread of COVID-19. In this paper, we provide an overview of the history and characteristics of the SARS-CoV-2 virus, the current global COVID-19 situation, the possible mechanisms of the deactivation of viruses by soaps, and the potential effectiveness of soap in eliminating coronaviruses including SARS-CoV-2.

Coronavirus disease 2019 (COVID-19) has been first appeared in Wuhan, China but its fast transmission, led to its widespread prevalence in various countries and make it a global concern. In addition, lack of a definitive treatment is another concern that needs to be attention. Researchers have come up with several options, which are not certain, but protease inhibitor and some antiviral agent are in the forefront. In this study a virtual screening procedure employing docking of different databases including 1615 FDA approved drugs was used to identify new potential small molecule inhibitors for protease protein of COVID-19. The docking result indicates that among all, simeprevir (Hepatitis C virus (HCV) NS3/4A protease inhibitor) could fit well to the binding pocket of protease and because of some other positive features including ADME profile, might be a helpful treatment option for COVID-19.

Background Oil palm (OP), Elaeis guineensis , is by far the most important global oil crop, supplying about 40% of total traded vegetable oil. Palm oils are key dietary components consumed daily by over three billion people, mostly in Asia, and also have a wide range of important non-food uses including in cleansing and sanitising products. Main body Oil palm is a perennial crop with a >25-year life cycle and an exceptionally small land footprint compared to annual oilseed crops. Oil palm crops globally produce an annual 81 million tonnes (Mt) of oil from about 19 million hectares (Mha). In contrast, the second and third largest vegetable oil crops, soybean and rapeseed, yield a combined 84 Mt oil but occupy over 163 Mha of increasingly scarce arable land. Despite this advantage, oil palm has acquired a poor environmental reputation, especially in Europe and North America, although soybean planting is now responsible for more deforestation. Oil palm crops face other challenges in the 2020s. On the demand side, these include changing consumer purchasing habits, threats to global trade systems, and diminishing demand for liquid fuels as transport systems become increasingly electrified. On the supply side, major issues include stagnant yields in ageing plantations, sluggish replanting of improved varieties, labour shortages, diseases and climatic/ environmental threats. The latter include the increasing incidence of new and existing pests/diseases and a general lack of climatic resilience, especially relating to elevated temperatures and increasingly erratic rainfall patterns. This review surveys the oil palm sector in the 2020s and beyond, its major challenges and options for future progress. Conclusions Oil palm crops face many future challenges, including emerging threats from climate change and new pests and diseases, that require more effective international collaboration. Nevertheless, new breeding technologies are providing the promise of improvements, such as much higher yielding varieties, improved oil profiles, enhanced disease resistance and modified crop architecture to enable harvesting mechanisation. The industry also needs to redouble its efforts to engage with global consumers in a constructive dialogue aimed at addressing its image problem and explaining the many benefits of its products.

Humanity’s social and economic development has been challenged by a range of adversities over the millennia that have caused widespread and unimaginable suffering. At the same time, these challenges have forced humans to evolve more wisely, overcoming adversity through creativity and leading to advancements in science and technology, medicine, ethics and legal systems, and socio-political systems. The dynamics of risks and opportunities caused by COVID-19, in the built, cyber, social and economic environments, present opportunities for deepening our understanding of resilient and sustainable development and infrastructure. This article reflects on five lessons that COVID-19 is teaching us about what it means to develop sustainably through the lens of transportation: (1) sustainable development planning and analytical frameworks must be comprehensive, for long-term sustainability; (2) multi-modal transportation is a superior vision for sustainable development than any one particular mode; (3) tele-activities are part of an effective infrastructure sustainability strategy; (4) economic capital is critically important to sustainable development even when it is not a critical existential threat, and, (5) effective social capital is essential in global disaster resistance and recovery, and can and must be leveraged between fast-moving and slow-moving disasters. Resilient and sustainable infrastructure will continue to be critical to addressing evolving natural and man-made hazards in the 21^st Century.

Purpose: Acute kidney injury (AKI) is a severe symptom of the 2019 novel coronavirus disease (COVID-19), especially for patients in a critical condition.This study explored the potential mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on AKI at the single-cell level. Methods: 15 normal human kidney samples were collected and analyzed using single-cell RNA sequencing (scRNA-seq). Subsequently, we analyzed the components and proportions of kidney cells expressing the host cellular receptor ACE2 and the key protease TMPRSSs family, and analyzed the expression differences in Occidental and Asian populations. Results: We drafted the currently available world's largest human kidney cell atlas with 42,589 cells and identified 19 clusters through unsupervised hierarchical clustering analysis. ACE2 and TMPRSSs genes were significantly co-expressed in podocytes and proximal convoluted tubules as potential host cells targeted by SARS-CoV-2. Comparative analysis showed that ACE2 expression in kidney cells was no less than that in the lung, esophagus, small intestine and colon, suggesting that the kidney may be an important target organ for SARS-CoV-2. In addition, given the high expression of ACE2 and kidney disease-related genes in Occidental donors relative to Asian donors, Occidental populations with SARS-CoV-2 infection might be a higher risk of of kidney injury.

The study sought to gauge the impact of COVID-19 pandemic in unleashing digital transformation in the education sector in South Africa. In order to gauge the impact, the study tracked the rate at which the 4IR tools were used by various institutions during the COVID-19 lockdown. Data were obtained from secondary sources, mainly newspaper articles, magazines and peer-reviewed journals. The findings are that, in South Africa, during the lockdown, a variety of 4IR tools were unleashed from primary education to higher and tertiary education where educational activities switched to remote learning (online learning). These observations point to the fact that South Africa generally has, some pockets of excellence to drive the education sector into the 4IR, which has the potential to increase access. Access to education, particularly at a higher education level, has always been a challenge due to a limited number of spaces available. Much as this pandemic has brought with it massive human suffering across the globe, there is an opportunity to assess successes and failures of deployed technologies, costs associated with them, and scaling these technologies to improve access.

As a result of the spread of SARS-CoV-2, a global pandemic was declared. Indiscriminate COVID-19 vaccination has been extended to include age groups and naturally immune people with minimal danger of suffering serious complications due to COVID-19. Solid immuno-histopathological evidence demonstrates that the COVID-19 genetic vaccines can display an off-target distribution in tissues that are terminally differentiated, triggering autoimmune reactions. These include the heart and brain, which may incur in situ production of spike protein eliciting a strong autoimmunological inflammatory response. Due to the fact that every human cell which synthesizes non-self antigens becomes inevitably the target of the immune system, and since the human body is not a strictly compartmentalized system, accurate pharmacokinetic and pharmacodynamic studies are needed in order to determine precisely which tissues can be harmed. Therefore, our article aims to draw the attention of the scientific and regulatory communities on the critical need of bio-distribution studies for the genetic vaccines against COVID-19, as well as of rational harm-benefit assessments by age group.

The current outbreak of the novel coronavirus also known as COVID-19 was declared as a public health emergency by the WHO where over a million people have been affected by the disease with over 50000 deaths till date. Social distancing is a method to minimize crowd interactions and prevent the spread of disease within groups of people. This is a common practice which has been carried out over generations to minimize the spread of virus by limiting its reproduction rate (R0) among communities. The article focuses on how social distancing has been used to deal previous pandemics globally and the issues that needs to be addressed to tackle the COVID-19 threat.

Coronavirus disease 2019 (COVID-19) was recently appeared all over the world. The viral main protease (3-chymotrypsin-like cysteine enzyme) controls COVID-19 duplication and manages its life cycle, making it a drug discovery target. Therefore, herein, we analyzed the theoretical approaches of 10 structurally different hydrolysable tannins as natural anti-COVID-19 through binding with the main protease of 2019-nCoV using molecular docking modelling via Molecular Operating Environment (MOE v2009) software. Our results revealed that there are top three hits may serve as potential anti-COVID-19 lead molecules for further optimization and drug development to control COVID-19. Pedunculagin, tercatain, and punicalin were found to faithfully interact with the receptor binding site and catalytic dyad (Cys145 and His41) of COVID-19 main protease, showing their successfully inhibit the protease enzyme of 2019-nCoV. We anticipated that this study would pave way for tannins based novel small molecules as more efficacious and selective anti-COVID-19 therapeutic compounds.

The novel respiratory disease COVID-19 has reached the status of worldwide pandemic and large efforts are currently being undertaken in molecularly characterizing the virus causing it, SARS-CoV-2. The genomic variability of SARS-CoV-2 specimens scattered across the globe can underly geographically specific etiological effects. In the present study, we gather the 48,635 SARS-CoV-2 complete genomes currently available thanks to the collection endeavor of the GISAID consortium and thousands of contributing laboratories. We analyze and annotate all SARS-CoV-2 mutations compared with the reference Wuhan genome NC_045512.2, observing an average of 7.23 mutations per sample. Our analysis shows the prevalence of single nucleotide transitions as the major mutational type across the world. There exist at least three clades characterized by geographic and genomic specificity. In particular, the clade G, prevalent in Europe, carries a D614G mutation in the Spike protein, which is responsible for the initial interaction of the virus with the host human cell. Our analysis may drive local modulation of antiviral strategies based on the molecular specificities of this novel virus.

The fast spread of COVID-19 constitutes a worldwide challenge to the public health, educational, and trade systems, affecting the overall wellbeing of human societies. The high transmission and mortality rates of this virus, and the unavailability of a vaccine or treatment, resulted in the decision of multiple governments to enact measures of social distancing. Thus, it is of general interest to consider the validity of the proposal for keeping a social distancing of at least 2 m from other persons to avoid the spread of COVID-19. The exposure to the bioaerosol can result in the deposition of the pathogen in the respiratory tract of the host causing disease and an immunological response. In the atmospheric context, the work evaluates the effect of aerodynamic diameter (size) of particles in carrying RNA copies of the novel coronavirus. A SARS-CoV-2 carrier person talking, sneezing, or coughing at distance of 2 m can still provide a pathogenic bioaerosol load with submicron particles that remain viable in air for up to 3 hours for exposure of healthy persons near and far from the source in a stagnant environment. The deposited bioaerosol creates contaminated surfaces, which if touched can act as a path to introduce the pathogen by mouth, nose, or eyes and cause disease.

Coronavirus-infected diseases have posed great threats to human health. In past years, highly infectious coronavirus-induced diseases, including COVID-19, SARS, and MERS, have resulted in world-wide severe infections. Our literature annotations identified 110 chemical drugs and 26 antibodies effective against at least one human coronavirus infection in vitro or in vivo. Many of these drugs inhibit viral entry to cells and viral replication inside cells or modulate host immune responses. Many antimicrobial drugs, including antimalarial (e.g., chloroquine and mefloquine) and antifungal (e.g., terconazole and rapamycin) drugs as well as antibiotics (e.g., teicoplanin and azithromycin) were associated with anti-coronavirus activity. A few drugs, including remdesivir, chloroquine, favipiravir, and tocilizumab, have already been reported to be effective against SARS-CoV-2 infection in vitro or in vivo. After mapping our identified drugs to three ontologies ChEBI, NDF-RT, and DrON, many features such as roles and mechanisms of action (MoAs) of these drugs were identified and categorized. For example, out of 57 drugs with MoA annotations in NDF-RT, 47 have MoAs of different types of inhibitors and antagonists. A total of 29 anticoronaviral drugs are anticancer drugs with the antineoplastic role. Two clustering analyses, one based on ChEBI-based semantic similarity, the other based on drug chemical similarity, were performed to cluster 110 drugs to new categories. Moreover, differences in physicochemical properties among the drugs were found between those inhibiting viral entry and viral replication. A total of 163 host genes were identified as the known targets of 68 anti-coronavirus drugs, resulting in a network of 428 interactions among these drugs and targets. Chlorpromazine, dasatinib, and anisomycin are the hubs of the drug-target network with the highest number of connected target proteins. Many enriched pathways such as calcium signaling and neuroactive ligand-receptor interaction pathways were identified. These findings may be used to facilitate drug repurposing against COVID-19.

The novel coronavirus, COVID-19 is now officially declared as a pandemic by the World Health Organization (WHO), and most parts of the world are taking drastic measures to restrict human movements to contain the infection. Like millions of others around the world, I am wondering, is there anything that could be done, other than keeping high personal hygiene, and be vigilant of symptoms, to reduce the chances of infection, or at least to reduce the burden of the disease. So far, the National and International health agencies, including the National Institutes of Health (NIH), the Centers for Disease Control and Prevention (CDC), and the WHO have provided clear guidelines for both preventive and treatment suggestions. In this opinion-based article, I want to discuss, why keeping the adequate micronutrient balance might enhance the host response and be protective of viral infections. A detailed in-depth discussion of various micronutrients is not the purpose of this article, I will mostly emphasize on the role of zinc in viral infection.

We are proposing, for any interested investigator, a randomized open clinical trial for mild and mild-to-moderate Covid-19 comparing a treatment regimen with standard of care, and eventually with another investigational regimen, if ongoing or will be implemented. The patients could be hospitalized or ambulatory but not requiring admission to intensive care units and mechanical ventilation. The proposed therapeutic regimen consists of doxycycline (an antimicrobial having also anti-inflammatory properties, probable antioxidant and possible some antiviral effects), and pentoxifylline, a hemorheological compound used in occlusive arterial diseases but also having proven anti-inflammatory properties. Doxycycline is included in the WHO’s list of essential medicine being an effective, safe, widely available, and inexpensive medication and widely accessible. It will be administered at a dosage of 100 mg orally twice daily for ten days. Pentoxifylline, in clinical use since 1972, and also widely accessible, will be given at a dosage of 400 mg orally, also twice daily, for ten days. The primary outcome measures are: 1) Progression of disease to a severe form requiring intensive care admission and mechanical ventilation; 2) Fatality rates and 3) Time to clinical recovery.This proposal was presented to the National Directors and Core Leads meeting of the Canadian Trials Network (CTN) on May 6, 2020. The interventional trial template suggested by CTN was used for designing the trial.

Understanding tourist behaviour during and after major tourism crises is essential to help destinations recover. The COVID-19 pandemic, a period of uncertainty and risk, makes it relevant to assess factors that influence travel intentions. There has been little research on tourist behaviour during health crises and, in particular, on perceived health risk and uncertainty effects on travel intentions. This study was carried out during the first months of the pandemic in Brazil and aims to investigate the role of health risk perception and intolerance of uncertainty on travel intentions for 2020 and 2021. We applied an online survey to 1,150 Brazilian participants from March to May of 2020. Our findings indicate that perceived COVID-19 severity, perceived probability of contracting it, and expected pandemic duration are significant predictors of travel intentions for both years. This paper sheds new light on tourist behaviour in the context of global health crises.

Public health practices including handwashing and vaccinations help reduce the spread and impact of infections. Nevertheless, the global burden of infection is high, and additional measures are necessary. Acute respiratory tract infections, for example, are responsible for approximately 2.65 million deaths per year. The role nutrition plays in supporting the immune system is well-established. A wealth of mechanistic and clinical data show that vitamins, including vitamins A, B6, B12, C, D, E, and folate; trace elements, including zinc, iron, selenium, magnesium, and copper; and the omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid play important and complementary roles in supporting the immune system. Inadequate intake and status of these nutrients are widespread, leading to a decrease in resistance to infections and as a consequence an increase in disease burden. Against this background the following conclusions are made: 1) Supplementation with the above micronutrients and omega-3 fatty acids is a safe, effective, and low-cost strategy to help support optimal immune function; 2) Supplementation above the RDA, but within recommended upper safety limits, for specific nutrients such as vitamins C and D is warranted; and 3) Public health officials are encouraged to include nutritional strategies in their recommendations to improve public health.

The objective of this study is to determine the impact of COVID-19 on the performance of Pakistani Stock Market. This study uses the data of COVID-19 related positive cases, fatalities, recovers and the closing prices of PSX 100 index of the first half of 2020. The findings of the study suggest that only COVID-19 recoveries are influencing the performance of the index and the daily positive cases and fatalities are insignificantly related to the performance. Further studies can be performed by incorporating other variables such as economic growth, interest rate and inflation rate along with the COVID-19 related variables at a cross-country level.

Corona virus disease 2019 (COVID-19) is caused by a Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2), which is a positive strand RNA virus. The SARS-CoV-2 genome and its association to SAR-CoV-1 vary from ca. 66% to 96% depending on the type of betacoronavirdeae family members. With several drugs, viz. chloroquine, hydroxychloroquine, ivermectin, artemisinin, remdesivir, azithromycin considered for clinical trials, there has been an inherent need to find distinctive antiviral mechanisms of these drugs. Curcumin, a natural bioactive molecule has been shown to have a therapeutic potential for various diseases, but its effect on COVID-19 has not been explored. In this study, we show the binding potential of curcumin targeted to a variety of SARS-CoV-2 proteins, viz. spike glycoproteins (PDB ID: 6VYB), nucleocapsid phosphoprotein (PDB ID: 6VYO), membrane glycoprotein (PDB ID: 6M17) along with nsp10 (PDB ID: 6W4H) and RNA dependent RNA polymerase (PDB ID: 6M71) structures. Our results indicate that curcumin has high binding affinity towards nucleocapsid and nsp 10 proteins with potential antiviral activity.

There were warnings before; nevertheless the current CoVID-19 pandemic took the world by surprise: within just four month, it conquered the globe and claimed over 200'000 lives. Unprecedented governmental actions put about half of the population under curfew or lock-down. The resulting economic meltdown is expected to eliminate globally 9’000’000’000’000 (9 trillion) USD in 2020 and 2021 alone, a value roughly the size of the yearly GDP of the world’s 150 smallest economies. The resulting crises might cause mass-unemployment and a hunger pandemic later this year. This Essay analyses current statistical data of the CoVID-19 pandemic to develop a guideline for a path through the crisis, minimizing both loss of lives and economic costs. Part 1 details the current situation; part 2 develops a small set of measures, allowing a near normal life until a future vaccination campaign has reached sufficient numbers of people; and part 3 provides some important lessons for the future beyond SARS-CoV-2. The Essay leads to the following key-messages: 1) The CoVID-19 pandemic will stay for at least two more years. This is the minimum time required for a vaccination campaign to reach sufficient numbers of people. 2) The crucial element to control the pandemic is keeping case numbers under the threshold required for a functional tracing, testing & isolation (TTI) strategy. That threshold differs from country to country and strongly depends on culture and the applied tracing technology as well as available testing capacities. 3) The economic burden of a TTI strategy is moderate while fatalities are also reduced. Hence, such an approach is strongly recommended. Its implementation requires a set of simple and cost-effective measures (see figure below), which in combination seem to be sufficient to keep CoVID-2’s reproductive rate at or below 1. 4) Implementing international coordination of actions will be necessary for effective infection-chain tracing5) If case numbers are above the TTI threshold, shutdown measures remain the only option until tracing of infection chains becomes feasible again.6) In the future, neglected pandemic-related research requires a funding boost. Just 1% of the bill of the current crisis could support the research of 45’000 scientist for 20 years.

Currently, there is no specific treatment for COVID-19 proven by clinical trials. WHO and CDC guidelines therefore endorse supportive care only. However, frontline clinicians have been applying several virus-based and host-based therapeutics in order to combat SARS-CoV-2. Medications from COVID-19 case reports, observational studies and the COVID-19 Treatment Guideline issued by the China's National Health Commission (7^th edition published March 3^rd, 2020. Edited translation attached) are evaluated in this review. Key evidence from relevant in vitro researches, animal models and clinical studies in SARS-CoV-2, SARS-CoV and MERS-CoV are examined. Antiviral therapies remdesivir, lopinavir/ritonavir and umifenovir, if considered, could be initiated before the peak of viral replication for optimal outcomes. Ribavirin may be beneficial as an add-on therapy and is ineffective as a monotherapy. Corticosteroids use should be limited without indicating comorbidities. IVIG is not recommended due to lack of data in COVID-19. Xuebijing may benefit patients with complications of bacterial pneumonia or sepsis. The efficacy of interferon is unclear due to conflicting outcomes in SARS and MERS studies. Chloroquine and hydroxychloroquine have shown in vitro inhibition of SARS-CoV-2 and may be beneficial as both prophylactic and treatment therapy. For patients who developed cytokine release syndrome, interleukin-6 inhibitors may be beneficial. Given the rapid disease spread and increasing mortality, active treatment with readily available medications may be considered timely prior to disease progression.

Coronavirus disease 2019 (COVID-19) can lead to systemic coagulation activation and thrombotic complications. We investigated the incidence of objectively confirmed venous thromboembolism (VTE) in 198 hospitalized patients with COVID-19 in a single-center cohort study. Seventy-four patients (37%) were admitted to the intensive care unit (ICU). At time of data collection, 58 (29%) were still hospitalized and 14% had died. During a median follow-up of 5 days (IQR, 3-9), 33 patients (17%) were diagnosed with VTE of whom 22 (11%) had symptomatic VTE, despite routine thrombosis prophylaxis. The cumulative incidences of VTE at 7 and 14 days were 15% (95% CI, 9.3-22) and 34% (95% CI, 23-46), respectively. For symptomatic VTE, these were 11% (95% CI, 5.8-17) and 23% (95% CI, 14-33). VTE appeared to be associated with death (adjusted HR, 2.9; 95% CI, 1.02-8.0). The cumulative incidence of VTE was higher in the ICU (25% at 7 days 95% CI, 15-36, and 48% at 14 days, 95% CI, 33-61) than on the wards (any VTE and symptomatic VTE 6.5 % at 7 days (95% CI, 1.5-17) and 10% at 14 days (95% CI, 2.9-24)).The observed risk for VTE in COVID-19 is high, particularly in ICU patients, which should lead to a high level of clinical suspicion and low threshold for diagnostic imaging for DVT or PE. Future research should focus on optimal diagnostic and prophylactic strategies to prevent VTE and potentially improve survival.

Globally, there is massive uptake and explosion of data and challenge is to address issues like scale, pace, velocity, variety, volume and complexity of this big data. Considering the recent epidemic in China, modeling of COVID-19 epidemic for cumulative number of infected cases using data available in early phase was big challenge. Being COVID-19 pandemic during very short time span, it is very important to analyze the trend of these spread and infected cases. This chapter presents medical perspective of COVID-19 towards epidemiological triad and the study of state-of-the-art. The main aim this chapter is to present different predictive analytics techniques available for trend analysis, different models and algorithms and their comparison. Finally, this chapter concludes with the prediction of COVID-19 using Prophet algorithm indicating more faster spread in short term. These predictions will be useful to government and healthcare communities to initiate appropriate measures to control this outbreak in time.

As early as February 2020, many countries have started imposing measures to curb the spread of Covid-19. Despite the right intention, it is a challenging moment for the people, especially the rural population living in the coastal areas. The document presents the preliminary findings on the impacts of Covid-19 on the small scale fisheries in Tun Mustapha Park, Sabah, Malaysia.

Reliable methods to confirm the diagnosis of COVID-19 are essential to the successful management and containment of the virus. Current diagnostic options are limited in type, supply, and reliability. This article explores the controversial unreliability of existing diagnostic methods and maintains that more reliable diagnostic methods, combinations, and sequencing are necessary to effectively assist in reducing the occurrence of discharge of the patient on false negative test results. This reduction would in effect reduce transmission of the disease.

Real-time estimation of the parameters characterising infectious disease transmission is important for optimization quarantine interventions during outbreaks. One of the most significant parameters is the effective reproduction number - number of secondary cases produced by a single infection. The current study presents an approach for estimating the effective reproduction number and its application to COVID-19 outbreak. The method is based on fitting SIR epidemic model to observation data in a sliding time window and allows to show real-time dynamics of reproduction number at any phase of epidemic for countries globally. Online data on COVID-19 daily cases of infections, recoveries, deaths are used.Finally, time-dependent reproduction number is explored in connection with dynamics of peoples mobility. The method allows to assess the disease transmission potential and understand the effect of interventions on epidemics spread. It also can be easily adapted to future outbreaks of different pathogens. The tool is available online as Python code from the Github repository.

As the coronavirus disease 2019 (COVID-19), which is caused by the novel SARS-CoV-2, continues to spread rapidly around the world, there is a need for well validated serological assays that allow the detection of viral specific antibody responses in COVID-19 patients or recovered individuals. In this study, we established and used multiple indirect Enzyme Linked Immunosorbent Assay (ELISA)-based serological assays to study the antibody response in COVID-19 patients. In order to validate the assays we determined the cut off values, sensitivity and specificity of the assays using sera collected from pre-pandemic healthy controls, COVID-19 patients at different time points after disease-onset, and seropositive sera to other human coronaviruses. The developed SARS-CoV-2 S1 subunit of the spike glycoprotein and nucleocapsid (N)-based ELISAs not only showed high specificity and sensitivity but also did not show any cross-reactivity with other CoVs. We also show that all RT-PCR confirmed COVID-19 patients tested in our study developed both virus specific IgM and IgG antibodies as early as week one after disease onset. Our data also suggest that the inclusion of both S1 and N in serological testing would capture as many potential SARS-CoV-2 positive cases as possible than using any of them alone. This is specifically important for tracing contacts and cases and conducting large-scale epidemiological studies to understand the true extent of virus spread in populations.

The current COVID-19 pandemic is one of the most devastating events in recent history. The virus causes relatively minor damage to young, healthy populations, imposing life-threatening danger to the elderly and people with diseases of chronic inflammation. Therefore, if we could reduce the risk for vulnerable populations, it would make the COVID-19 pandemic more similar to other typical outbreaks. Children don’t suffer from COVID-19 as much as their grandparents and have a much higher melatonin level. Bats are nocturnal animals possessing high levels of melatonin, which may contribute to their high anti-viral resistance. Viruses induce an explosion of inflammatory cytokines and reactive oxygen species, and melatonin is the best natural antioxidant that is lost with age. The programmed cell death coronaviruses cause, which can result in significant lung damage, is also inhibited by melatonin. Coronavirus causes inflammation in the lungs which requires inflammasome activity. Melatonin blocks these inflammasomes. General immunity is impaired by anxiety and sleep deprivation. Melatonin improves sleep habits, reduces anxiety and stimulates immunity. Fibrosis may be the most dangerous complication after COVID-19. Melatonin is known to prevent fibrosis. Mechanical ventilation may be necessary but yet imposes risks due to oxidative stress, which can be reduced by melatonin. Thus, by using the safe over-the-counter drug melatonin, we may be immediately able to prevent the development of severe disease symptoms in coronavirus patients, reduce the severity of their symptoms, and/or reduce the immuno-pathology of coronavirus infection on patients’ health after the active phase of the infection is over.

The global pandemic caused by the new SARS-COV-2 coronavirus makes it necessary to search for drugs for its control. Within of this research it has been known that the ivermectin drug, a FDA-approved drugs which is formulated as an 80:20 mixture of ivermectin B1a and B1b and used commonly for parasitic infections, has an inhibitory effect on viruses, includes SARS-COV-2 at in vitro level. In the particular case of SARS-COV-2 its mechanism of action remains elusive and controversial. Interestingly, the energy of interaction of ivermectin with any of the proteins the SARS-CoV-2 and the possible structural alterations at the protein level that this drug can cause have not been reported. In this sense, we carried out a bioinformatics study with docking strategies and molecular dynamics to predict the binding and disturbance induced by ivermectin in proteins associated with SARS-CoV-2. We use DockThor and Molegro docking scores. The DockThor server and myPresto software were used to build complexes and dynamics studies, respectively. The results obtained suggested that ivermectin is capable of docking with the 3CL protease and the HR2 domain, and may promote structural changes in these proteins by inducing unfolding/folding. Specifically, ivermectin brings protease to a significantly more deployed conformational state and the HR2 domain to a more compact state compared to the native state. Finally, it is shown that B1a and B1b macrocyclic lactones have a behavior different from to each target protein. These results suggest a possible inhibitory effect against SARS-CoV-2 due to a synergistic role of this drug to spontaneously bind to two important proteins involve in the proliferation of this virus. However, more studies are required on this possible mechanism of action.

An outbreak of a pandemic COVID-19 disease caused by a novel coronavirus SARS-CoV-2 has posed a serious threat to human health and the economy of the whole world. Bangladesh is one of the most densely populated countries in the world, which has also come under the attack of this viral disease. This perspective report aimed to describe the responses of Bangladesh to tackle the COVID-19, particularly on how Bangladesh is dealing with this novel viral disease with limited resources. The first case of a COVID-19 patient was detected in Bangladesh on March 8, 2020. Since then, a total of 2,144 peoples are officially reported as COVID-19 infected with 84 deaths. To combat the COVID-19, the government has taken various steps to tackle the epidemic outbreak of it such as diagnosis of the suspected cases, quarantine of doubted people and isolation of infected patients, local or regional lockdown, grant general leave from all offices for staying home of people, increase public awareness and enforce social distancing and so on. In addition, to address the socio-economic situations, the government announced several financial stimulus packages of about USD 11.17 billion. However, very limited diagnostic facilities, health workers, resources such as hospital beds, personal protective equipment, intensive care unit, and ventilators in the hospitals along with limited public unawareness are the major challenges for Bangladesh to tackle the situation effectively. This report described the responses of Bangladesh to tackle the COVID-19 and discusses prevailing challenges to mitigate this highly contagious disease with limited resources.

In the end of April nearly 100 cases of children aged between 6 month and 9 years with Kawasaki like disease were reported (mostly in Europe) probably linked to COVID-19. With the increasing awareness of this condition the number of cases reported is increasing worldwide. We aim to sum up the known data about this new entity based on published data (in a case report, a series of 8 cases and in newspapers and society statement) and using our knowledge of classical Kawasaki disease. It seems to be a post infectious disease with an onset between 2-4 weeks after the infection, probably in genetically predisposed children aged between 6 month to 17 years. A very rough estimation of incidence based on current data from Bergamo, Italy, and New York State and a lot assumption is between 0.016% (95% CI:0.013-0.02%) - 0.31% (95% CI: 0.2-0.47%) of infected children. Clinical signs overlaps with Kawasaki disease in some children, but another feature is prominent gastrointestinal manifestations. For the 9 detailed patients most had incomplete presentation for Kawasaki disease (with a mean 1.7 (+/-1.2) criteria per patient for the 5 non fever criterion) and only one had a classical form. In some cases, presentation is closer to toxic shock syndrome or isolated myocarditis. Persistent fever seems to be constant and biological exploration are consistent with inflammation (elevated CRP, ferritin and D-Dimers). Management is described as supportive and children seem to improve rapidly, but can require cardiac or respiratory support. In date of 11 may 2020 there is 4 deaths confirmed linked to these new entities (1 in UK and 3 in New York). Paediatricians and general practitioners need to be aware of these possible evolution following COVID-19 infection. However it seems to be rare and children are probably still spared from most morbidities and mortality linked to COVID-19 infection .There are need of published detailed cohorts to better delineate these entities.

Nowadays tourism is growing as a gigantic, global business accounting for 10.4 % of Global GDP and 10% of global employment (Joppe, 2020). This review paper aims to explore the risks borne for tourism sector by the outbreak of corona-virus in 2020. Tourism sector is a highly vulnerable sector and the costs that will be borne from corona-virus pandemic will be devastating, particularly for the countries relying on this sector as a basic source of income. The paper suggests possible solutions and adaptation routes, while at the same time reviews lessons of the past from other pandemics and crisis. This paper is very useful for tourism policy makers and governments in countries where tourism contributes a significant part of their GDP, but also for other economic sectors closely but indirectly connected in the tourism value chain.

We applied a generalized SEIR epidemiological model to the recent SARS-CoV-2 outbreak in the world, with a focus on Italy and its Lombardia, Piemonte, and Veneto regions. We focus on the application of a stochastic approach in fitting the model numerous parameters using a Particle Swarm Optimization (PSO) solver, to improve the reliability of predictions in the medium term (30 days). We analyze the official data and the predicted evolution of the epidemic in the Italian regions, and we compare the results with data and predictions of Spain and South Korea. We link the model equations to the changes in people’s mobility, with reference to Google’s COVID-19 Community Mobility Reports. We discuss the effectiveness of policies taken by different regions and countries and how they have an impact on past and future infection scenarios.

SARS-CoV-2 or COVID-19, a new seventh human corona virus, has out-broken in Wuhan, China since 31^st December 2019, and quickly escalated to take the form of pandemic which killed many human beings throughout almost all countries across continents. The rapidity of its transmission from human to human is far greater than all previous human corona viruses which came into existence like SARS-CoV, MERS-CoV, etc. The nucleotide sequence of SARS-CoV-2 (isolates Wuhan-Hu-1) is 29,875 bp in ss-RNA. Symptoms of SARS-CoV-2 infected pneumonia include from asymptomatic to high fever and/or respiratory illnesses. Coronavirus virion (spherical/round /elliptical in shape) consists of three parts- outer membrane or envelope, nucleocapsid and genome (RNA). SARS-CoV-2 was shown to use receptor, angiotensin converting enzyme 2 (ACE2) for attachment to the cells through its surface spike (S) protein (S1), and the virion enters into the host cell through two routes- direct membrane fusion and endocytotic pathway. The RNA of SARS-CoV acts directly as mRNA and here minus(-) 1 programmed ribosomal frameshift (-1PRF) is being operated by slippery sequence and pseudoknot, so it translates 16 nonstructural proteins including RNA dependent RNA replicase. Then genomic RNA replicated continuously on – strand RNA template and subgenomic RNA transcribed discontinuously on –RNA template to sgmRNA. Subgenomic RNAs/sgmRNAs synthesize all structural proteins. This article takes into consideration the details of established theories of viral structure, viral attachment, mode of entry into human cells, different models of replication and transcription of virus genome proposed by eminent scientists over the years, and makes an in depth examination highlighting meaningful points or important target cites of viral propagation or synthesis, which are conserved, for prompt development of potent drugs or vaccine to counter COVID-19 for which human race is anxiously and eagerly waiting.

Rapidly spreading disease, COVID-19 is classified as the human-to-human transmission-able disease and currently is a pandemic in the Globe. In this paper, we propose conceptual mathematical models for COVID-19 outbreak and it's control measurement; quarantine, hospitalization and the effect of panic and anxiety. In this situation, mathematical models are a important tool to employ an effective strategy in order to fight against this pandemic. We establish the positivity and boundedness of solutions, local and global stability analysis of equilibria to examine its epidemiological relevance. To validate the model and estimating the important model parameters and prediction about the disease, we consider the real cases of Italy from $15^{th}$ Feb to $13^{th} $ April 2020. In a series of graphical map, we have presented the comparative study to estimate the current scenarios and to predict the control measurement time boundary of the outbreak.

The SARS-CoV-2 was confirmed to cause the regional outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China. The 3C-like protease (3CL^pro), an essential enzyme for viral replication, is a valid target to compacts SARS-CoV and MERS-CoV. In this research, an integrated library consisting of 1000 compounds from Asinex Focused Covalent (AFCL) library and 16 FDA-approved protease inhibitors were screened against SARS-CoV-2 3CL^pro. Top compounds with significant docking scores and making stable interactions with catalytic dyad residues were obtained. The screening results in identification of compound 621 from AFCL library as well as Paritaprevir and Simeprevir from FDA-approved protease inhibitors as potential inhibitors of SARS-CoV-2 3CL^pro. The mechanism and dynamic stability of binding between the identified compounds and SARS-CoV-2 3CL^pro were characterized using 50 nanoseconds (ns) molecular dynamic (MD) simulation approach. The identified compounds are potential inhibitors worthy of further development as SARS-CoV-2 3CLpro inhibitors/drugs. Importantly, the identified FDA-approved therapeutics could be ready for clinical trials to treat infected patients and help to curb the COVID-19.

The current Coronavirus Disease 19 (COVID-19) pandemic, caused by the SARS-CoV-2 virus, is unprecedented in recent history and threatens the lives and livelihoods of billions worldwide. The rapid spread and lack of modern parallels have left governments, health agencies, and the public racing to understand how to best mitigate and ultimately suppress the pandemic, but we are still working to understand the strengths and weaknesses of various interventions at our disposal. Few issues have been as contentious as the public use of face masks to control the pandemic’s spread. There is ongoing debate about their effectiveness, but an increasing body of evidence suggests that masks could be a useful in preventing the spread of coronavirus, leading several governments and health agencies to review and revise their policies. Here, we review the theory and evidence behind use of masks. The theory behind masks is that they prevent the spread of viral particles by infected persons, and inhalation of viral particles by uninfected persons. Even assuming masks are not 100% effective in preventing infection, they may reduce severity of infection by reducing viral dosing. Laboratory studies suggest masks may be effective in stopping both exhalation and inhalation of viral particles. However, real-world studies provided limited evidence for the use of masks in controlling influenza transmission and highlight potential problems associated with their misuse, such as poor compliance or improper use. Evidence for efficacy of face masks against the first SARS virus, SARS-CoV-1, implies that they may be effective against the current outbreak of SARS-Cov-2 virus. This is important as mathematical modeling suggests that even small reductions of in transmission rates can make a large difference over time, potentially slowing the pace of viral pandemics and limiting their spread. Perhaps the strongest argument for the use of masks is that countries with early adoption of masks have tended to see flatter pandemic curves, even without strict nationwide lockdowns. There is little evidence that respirators are more effective than surgical masks, but this may be due to misuse or poor compliance. Studies suggest some non-medical masks perform on par with medical masks. Improvised masks are less effective than medical masks, but may provide better protection than nothing at all. While many governments now encourage the use of improvised face coverings, more will need to be known about material, design, and who needs to wear masks, and when, to ensure effectiveness. Proper use of masks will also be important; if masks are used improperly or infrequently they may provide limited protection. It is important that public health policy makers consider the debate and the potential of masks as part of multi-faceted coronavirus control strategies.

Global pandemic COVID-19 is in stage 4 of widespread local transmission in Bangladesh- the country which did not have a noteworthy health policy and legislative structures to combat COVID-19 like a pandemic. Early strategic planning and groundwork for evolving and established challenges are crucial to assemble resources and react in an appropriate timely manner. This article, therefore, focuses on the public perception of comparative lockdown scenario analysis and how they may affect the sustainable development and the strategic management regime of COVID-19 pandemic in Bangladesh socioeconomically. Response from 159 respondents was collected via a purposive sampling survey method through a questionnaire, and 54 statements were collected for scenario analysis. Datasets were analyzed through a set of statistical techniques including Principal Component Analysis (PCA), hierarchical Cluster Analysis (CA), Pearson’s correlation matrix (PCM), Linear regression analysis (LRA), and psychometric characteristics were included in the Classical Test Theory (CTT) analysis. There were good associations among the lockdown scenarios and response strategies to be formulated. A strong significant positive relationship was observed between people who will start moving towards regular life and the formal and informal economic activities will be started in lockdown scenario 1(r=0.671, p<0.01). The scenario one describes how the death and infection rate will increase if Govt withdraw the partial lockdown before 40 to 50 days. Scenario 2 outlines people’s movement will enable low-level community transmission of COVID-19 with the infection and death rate will increase slowly (r=0.540, p<0.01). Moreover, there will be less supply of necessities of daily use with a price hike (r= 0.680, p<0.01). Scenario 3, full lock down will reduce the community transmission and death from COVID-19 (r=0.545, p<0.01). Moreover, along with the other problems gender discrimination and gender-based violence will increase rapidly (r=0.661, p<0.01). Form regression analysis, due to full lockdown, the formal and informal business, economy and education sector will be hampered severely (R=0.695), there was a strong association between the loss of livelihood and unemployment rate will increase due to business shutdown (p<0.01) and poor communities both in urban and rural areas will be affected severely (p<0.01).All these will further aggravate the humanitarian needs of the most vulnerable groups in the country in the coming months to be followed which needs to be dealt with proper response plans. It will undoubtedly affect the targets of global sustainable development goals (SDGs) of 2030 and all other development targets.

The global spread of coronavirus disease (COVID -19) worldwide has had a significant effect on social and economic growth. The contamination keeps on advancing quickly and eccentrically, representing a significant test to its recognition and conclusion. Coronaviruses are commonly recognized by seclusion from tests, regardless of whether natural or clinical, utilizing some atomic science procedures, which can take a few days. In this work an analytical review of virus transmission, methods of diagnosing COVID -19 using artificial intelligence techniques to classify images and types of biosensors. At long last, the deformities and points of interest of each kind of sensor are recognized and examined. This exploration gives an explanatory audit of the utilization of crown infection COVID-19 in 2019. Related examinations were led utilizing five dependable databases, for example, Science Direct, IEEE Xplore, Scopus, Web of Science, and PubMed. An acceptable investigation is remembered for this audit, which can be depended upon as a logical database to put resources into another technique for recognizing COIVD-19.

Spike (S) protein of Coronaviruses help in receptor attachment and virus entry into the host cells. While S protein is required for virus entry, it is also important as an immunogen as it is the most accessible part of the virus architecture. S protein form knob like structures (viral spikes) protruding outwards in the form of homotrimers containing an S1 and S2 as monomers. Mutations in structural proteins of virus play crucial role in determining virulence and also in many instances influencing emergence of antibody escape variants and cellular tropism. In this paper we have performed in depth analyses of spike protein sequences from various parts of the world and tried to correlate the data with possible functional relevance of such mutations.

New coronavirus (SARS-CoV-2) treatments and vaccines are under development to combat the COVID-19 disease. Several approaches are being used by scientists for investigation including 1) various small molecule approaches targeting RNA polymerase, 3C-like protease, and RNA endonuclease and 2) exploration of antibodies obtained from convalescent plasma from patients who have recovered from COVID-19. The coronavirus genome is highly prone to mutations that lead to genetic drift and escape from immune recognition; thus, it is imperative that sub-strains with different mutations are also accounted for during vaccine development. As the disease has grown to become a pandemic, new B-cell and T-cell epitopes predicted from SARS coronavirus have been reported. Using the epitope information along with variants of the virus, we have found several variants which might cause drifts. Among such variants, 23403A>G variant (p.D614G) in spike protein B-cell epitope is observed frequently in European countries such as the Netherlands, Switzerland and France.

Less aligned emphasis has been given to the COVID-19 infodemic coordinating with the COVID-19 outbreak. Global profusion of tangled monikers and hashtags has found their ways in daily communication and contributed to backlash against Chinese. Official naming efforts against infodemic should be meet with a fair share of identification. Based on brief critical reviews on previous multifarious naming practices, we punctuate heuristic introspection in scientific conventions and sociocultural paradigms. Infodemiological analysis promises to articulate that people around the globe are divided in their favor stigmatized monikers in the public and scientific communities because of perceptual bias. There is no positive correlation between the degree of infection in their territories and collective perceptual bias to COVID-19. The official portfolio “COVID-19” and “SARS-CoV-2” has not become de facto standard usages, but full-fledged official names are excepted to duly contribute to the resilience of negative perceptual bias and collective behavioral propensities.

The SARS-CoV-2 is a recently identified positive sense single stranded RNA virus and member of the coronavirus family of viruses. It is thought to be the etiological factor for the ongoing COVID-19 pandemic. This virus is thought to have originated from bats and acquired ability of human-to-human transmission. While SARS-CoV-2 is relatively benign, it has infected more than half a million people (as of March 29^th 2020) worldwide and the number of infected people continues to rise. More than 170 countries have reported COVID-19 positive cases. With a mortality rate of less than both the previous coronavirus outbreaks, COVID-19 has (conversely) caused the death of over 33,980 (as of 29^th March, 2020 at 22.00 hours EDT) people worldwide and the number is increasing. Given the enormous impact of this virus on human health and wellbeing and consequent devastating impacts on world trade, economics and quality of life, it is important to understand this virus better and get insight into its pathogenic mechanisms which will aid in devising effective measure to curb its spread and predict future pattern of its interaction with humans. Though very little is known about this SARS-CoV-2 but its mechanisms and patterns of spread can be speculated (with caution, nevertheless) from what we know about its closest relatives SARS-CoV-1 (responsible for SARS-2002 epidemic) and MERS-CoV (responsible for MERS-2012 epidemic). In the present review, we aim at bringing together the coherent and peer reviewed literature about the SARS-CoV-2 and its close relatives and try to understand its infection patterns and reconstruct its pathogenic mechanisms with anecdotes on diagnosis and future directions. We hope that this paper will serve the purpose of being a reliable source of information to scientists, clinicians and general public.

One notable features of the SARS-CoV-2 genome is that the spike protein of SARS-CoV-2 has a functional polybasic (furin) cleavage site (RRAR) at the S1–S2 boundary through the insertion of 12 nucleotides encoding PRRA. To date, the furin cleavage site (FCS) remains an experimentally uncharted territory both structurally and functionally. For instance, whether or not FCS is actually cleaved, before or after viral cell entry or exit, still remains to be experimentally investigated. With currently available structural data, this article presents a computational structural characterization of the FCS inserted into SARS-CoV-2 spike glycoprotein, and puts forward a set of structural hypothesis against the hypothesis of SARS-CoV-2 from purposeful manipulation: (1), the inserted FCS does not alter, neither stabilize nor de-stabilize, the overall structure of SARS-CoV-2 spike glycoprotein; (2), the net structural consequence of FCS is the insertion of a furin cleavage site into SARS-CoV-2 spike glycoprotein, whose S1 and S2 subunits will still be bonded together even if the FCS is actually cleaved by furin protease.

The world is facing a major health crisis, the global pandemic of COVID-19 caused by the SARS-CoV-2 coronavirus, for which no approved antiviral agents or vaccines are currently available. Here we describe a collection of codon-optimized coding sequences for SARS-CoV-2 cloned into Gateway-compatible entry vectors, which enable rapid transfer into a variety of expression and tagging vectors. The collection is freely available via Addgene. We hope that widespread availability of this SARS-CoV-2 resource will enable many subsequent molecular studies to better understand the viral life cycle and how to block it.

With the current rapid spread of COVID-19, global health systems are increasingly overburdened by the sheer number of people that need diagnosis, isolation and treatment. Shortcomings are evident across the board, from staffing, facilities for rapid and reliable testing to availability of hospital beds and key medical-grade equipment. The scale and breadth of the problem calls for an equally substantive response not only from frontline workers such as medical staff and scientists, but from skilled members of the public who have the time, facilities and knowledge to meaningfully contribute to a consolidated global response. Here, we summarise community-driven approaches based on Free and Open Source scientific and medical Hardware (FOSH) currently being developed and deployed to bolster access to personal protective equipment (PPE), patient treatment and diagnostics.

The COVID-19 pandemics has had an unprecedented global impact, and the COVID-19 mass vaccination campaign has been commonly regarded as crucial to overcome the pandemics. Since all-cause mortality is the best way to measure the consequences of a health intervention, the present study was devised to analyze the all-cause mortality data of the United Kingdom (UK), which are made publicly available broken down by vaccination status. Data from January to May 2022 were retrospectively collected and analyzed according to age groups and vaccination status and the relative risk (RR) for all-cause mortality was calculated in comparison to the corresponding unvaccinated groups. All-cause mortality RR was also calculated from January to May 2021 for vaccinated people. Results show that the all-cause mortality RR was higher in people who received one or two doses of COVID-19 vaccines throughout the whole period and in any of the age groups considered. People vaccinated with three doses more than 21 days earlier had RRs lower than unvaccinated people, which however linearly increased over time. RR in vaccinated people of all ages in comparison to unvaccinated people were lower in January-May 2021, however they steadily grew over time. The finding that all-cause mortality RR in vaccinated in comparison to unvaccinated people increases over time requires careful examination to understand the underlying factors. Meanwhile, all the other major countries should undertake a systematic collection of all-causes mortality broken down by vaccination status, and mass vaccination campaigns should be suspended.

The beginning of 2020 has seen the emergence of coronavirus outbreak caused by a novel virus called SARS-CoV-2. The sudden explosion and uncontrolled worldwide spread of COVID-19 show the limitations of existing healthcare systems to timely handle public health emergencies. In such contexts, innovative technologies such as blockchain and Artificial Intelligence (AI) have emerged as promising solutions for fighting coronavirus epidemic. On the one hand, blockchain can combat pandemics by enabling early detection of outbreaks, protecting user privacy, and ensuring reliable medical supply chain during the outbreak tracking. On the other hand, AI provides intelligent solutions for identifying symptoms caused by coronavirus for treatments and supporting drug manufacturing. Motivated by these, in this paper we present an extensive survey on the use of blockchain and AI for combating coronavirus (COVID-19) epidemics based on the rapidly emerging literature. First, we introduce a new conceptual architecture which integrates blockchain and AI specific for COVID-19 fighting. Particularly, we highlight the key solutions that blockchain and AI can provide to combat the COVID-19 outbreak. Then, we survey the latest research efforts on the use of blockchain and AI for COVID-19 fighting in a wide range of applications. The newly emerging projects and use cases enabled by these technologies to deal with coronavirus pandemic are also presented. Finally, we point out challenges and future directions that motivate more research efforts to deal with future coronavirus-like epidemics.

Smoking is a risk factor for respiratory infections and there is reasonable concern that it may affect COVID-19 susceptibility and severity. Recent studies have focused on the interaction between smoking (and nicotine) and ACE2 expression, suggesting that ACE2 up-regulation could contribute to enhanced viral cell entry. However, case series have shown that there is an unexpectedly low prevalence of smoking among hospitalized COVID-19 cases. Since early April, we were the first to hypothesize that dysfunction of the nicotinic cholinergic system (NCS) may be implicated in the pathophysiology of severe COVID-19. We recently reported that many of the clinical manifestations of severe COVID-19 could be explained by dysregulation of the NCS. In this study, we present an amino acid sequence in the receptor binding domain of the SARS-CoV-2 Spike glycoprotein which is homologous to a sequence of a snake venom toxin. We present the 3D structural location of this “toxin-like” sequence on the Spike Glycoprotein. These findings suggest that SARS-CoV-2 could potentially interact with acetylcholine receptors causing dysregulation of the NCS and the cholinergic anti-inflammatory pathway.

This paper is purposed to delineate the current situation around Bangladesh as well as impacts of Coronavirus Disease-2019 (COVID-19) around the country and how the people over here are encountering this threatening pandemic. COVID-19 is an international epidemic that has got rapid wide-spread throughout different countries of the world to date. After its first outbreak in China different continents started to make sense and get aware against COVID-19 though, due to its special strategy of transmission several countries have been quite deteriorated preventing it. All the countries are moving at their best forward to find out any solution so that whole world could get rid of this horrifying situation as soon as possible. The authors here have reported an overview of how the outbreak of COVID-19 had put its commence in Bangladesh and to date how people over here have been tracing the way to tackle this havoc. Also, the changes that have brought around due to the crisis have offered us some fertile lessons that are enunciated here by the authors. To conclude, special considerations are anticipated to be highlighted pertaining COVID-19 outbreak in Bangladesh.

There is an urgent need to advance safe and affordable COVID-19 vaccines for low- and middle-income countries of Asia, Africa and Latin America. Such vaccines rely on proven technologies such as recombinant protein-based vaccines to facilitate its transfer for emerging market vaccine manufacturers. Our group is developing a two-pronged approach to advance recombinant protein-based vaccines to prevent COVID-19 caused by SARS CoV2 and other coronavirus infections. One vaccine is based on a yeast-derived (Pichia pastoris) recombinant protein comprised of the receptor binding domain (RBD) of the SARS-CoV formulated on alum and referred to as the CoV RBD219-N1 Vaccine. Potentially this vaccine could be used as a heterologous vaccine against COVID-19. A second vaccine specific for COVID-19 is also being advanced using the corresponding RBD of SARS-CoV-2. The first antigen has already undergone cGMP manufacture and is therefore “shovel ready” for advancing into clinical trials, following vialing and required GLP toxicology testing. Evidence for its potential efficacy to cross-protect against SARS-CoV-2 includes cross-neutralization and binding studies using polyclonal and monoclonal antibodies. Evidence in support of its safety profile include our internal assessments in a mouse challenge model using a lethal mouse adapted SARS strain, which show that SARS-CoV RBD 291N1 (when adsorbed to Alhydrogel®) does not elicit eosinophilic lung pathology. Together these findings suggest that recombinant protein-based vaccines based on the RBD warrant further development to prevent SARS, COVID-19 or other coronaviruses of pandemic potential.

Nearly three months have passed since the emergence of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), which caused the rapidly spreading Coronavirus Disease 2019 (COVID-19) pandemic. To date, there have been more than 550,000 confirmed cases and more than 25,000 deaths globally caused by COVID-19. Chinese health authorities, where the virus emerged, have taken prompt strict public health measures to control and prevent the spread of the outbreak. In the kingdom of Saudi Arabia, unprecedented precautionary strict measures were applied to slow virus entry and to mitigate the risk of the outbreak. Here, we review the experience learned during the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) epidemic in Saudi Arabia, which has been in the country since 2012, and is expected to have helped the country to be well prepared for the current COVID-19 pandemic. We also discuss the country readiness, improvement in research and development, and the unprecedented rapid precautionary measures that have been taken by the Saudi government thus far.

Since the outbreak of the COVID-19 (Coronavirus Disease 19) pandemic, researchers have been trying to investigate several active compounds found in plants that have the potential to inhibit the proliferation of SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2). The present study aimed to evaluate bioactive compounds found in plants by using a molecular docking approach to inhibit the Main Protease (M^pro) and Spike (S) glycoprotein of SARS-CoV-2. The evaluation was performed on the docking scores calculated using AutoDock Vina as a docking engine. A rule of five (RO5) was calculated to determine whether a compound meets the criteria as an active drug orally in humans. The determination of the docking score was done by selecting the best conformation of the protein-ligand complex that had the highest affinity (most negative Gibbs' free energy of binding / ΔG). As a comparison, nelfinavir (an antiretroviral drug), chloroquine and hydroxychloroquine sulfate (anti-malarial drugs recommended by the FDA as emergency drugs) were used. The results showed that hesperidin, nabiximols, pectolinarin, epigallocatechin gallate, and rhoifolin had better poses than nelfinavir, chloroquine, and hydroxychloroquine sulfate as spike glycoprotein inhibitors. Hesperidin, rhoifolin, pectolinarin, and nabiximols had about the same pose as nelfinavir, but were better than chloroquine and hydroxychloroquine sulfate as M^pro inhibitors. These plant compounds have the potential to be developed as specific therapeutic agents against COVID-19. Several natural compounds of plants evaluated in this study showed better binding free energy compared to nelfinavir, chloroquine, and hydroxychloroquine sulfate which so far are recommended in the treatment of COVID-19. As judged by the RO5 and previous study by others, the compounds kaempferol, herbacetin, eugenol, and 6-shogaol have good oral bioavailability, so they are also seen as promising candidates for the development lead compounds to treat infections caused by SARS-CoV-2.

The spread of the global COVID-19 pandemic, the lack of specific treatment and the urgent situation requires use of all resources to remedy this scourge. In the present study, using molecular docking, we identify new probable inhibitors of COVID-19 by molecules from Nigella sativa L, which is highly reputed healing herb in North African societies and both Islamic and Christian traditions. The discovery of the M^pro protease structure in COVID-19 provides a great opportunity to identify potential drug candidates for treatment. Focusing on the main proteases in CoVs (3CL^pro/M^pro) (PDB ID 6LU7 and 2GTB); docking of compounds from Nigella Sativa and drugs under clinical test was performed using Molecular Operating Environment software (MOE). Nigelledine docked into 6LU7 active site gives energy complex about -6.29734373 Kcal/mol which is close to the energy score given by chloroquine (-6.2930522 Kcal/mol) and better than energy score given by hydroxychloroquine (-5.57386112 Kcal/mol) and favipiravir (-4.23310471 kcal/mol). Docking into 2GTB active site showed that α- Hederin gives energy score about-6.50204802 kcal/mol whcih is better energy score given by chloroquine (-6.20844936 kcal/mol), hydroxychloroquine (-5.51465893 kcal/mol)) and favipiravir (-4.12183571kcal/mol). Nigellidine and α- Hederin appeared to have the best potential to act as COVID-19 treatment. Further, researches are necessary to testify medicinal use of identified and to encourage preventive use of Nigella Sativa against coronavirus infection.

Decisions affecting the COVID-19 pandemic, by the individual and those with highest authority, are being made on the basis of unreliable data. Data about cases and deaths are collected daily but represent only a sample of reality. Statistics convert sample data into more reliable estimates. However, statistics have no magical powers; reliability requires dependable data. It is futile to rail against this darkness; COVID-19 is not a scientific experiment. However, we must do better both with data collection and data analysis. In this review, I focus on one element of the data, the asymptomatic case of COVID-19. Without reliable information about this number, decision makers are significantly blinded. By its nature, the asymptomatic case is hidden but contaminating to understanding COVID-19. The true case rate and death rate per case are unknowable without knowing the fraction of cases that are asymptomatic. The best estimate of asymptomatic cases is in the CDC document: COVID-19 Pandemic Planning Scenarios. For four different scenarios the estimates range from 10% to 70%, with the best estimate of 40% for asymptomatic cases. However, even the definition of the asymptomatic case is problematic. In simplest terms, two elements are required: an infection and no symptoms. How is “no symptoms” to be usefully defined? It appears to be analogous to pontificating about black swans from studying only white swans. It implies infection, but how is infection defined? Is it presence of the virus, replication of the virus, or presence of antibodies? Is asymptomatic disease an oxymoron? Without extensive, purposeful screening for specifically defined, essential symptoms and appropriate virus and antibody testing over time, the class of asymptomatic cases remains unknown. Current estimates range from <20% to ˃80%. If low, it can be ignored; if high, it dramatically and proportionately lowers the case rate and the death rate per case. Consequentially, the asymptomatic rate dramatically affects our societal and political responses. In this focused review, we assess the limitations of the published estimates, bring attention to the importance of obtaining accurate data, and exhort that high priority be given in the scientific community to understanding the issue, asymptomatic COVID-19 cases.

The novel coronavirus (2019-nCoV) is a human and animal pathogen recently emerged in the city of Wuhan in Hubei province of China, causing a spectrum of severe respiratory illnesses. Corona viruses makes entry in to human cells through its spike (S) protein that binds to cell surface receptors. Wide spread of 2019-nCoV has been attributed to relatively high affinity of S protein to its receptor. Although S protein is a highly importantdrug target, unavailability of a high-resolution crystal structure and solvent accessible binding surface has made it a tedious target for current rapid virtual screening. A homology model of the receptor binding domain (RBD) of 2019 -n CoV S protein that is reasonably acceptable for drug screening was prepared using a high resolution crystal structure of SARS corona virus (SARS CoV)S protein. Data obtained from RBD- receptor docking experiments and published molecular dynamics experiments were used to map a RBD-receptor interaction hotspot that can be used for designing small molecule inhibitors. The hot spot was then used for virtual screening of more than 3000 drugs approved by U.S Food and Drug Administration (FDA) and other authorities for human use. Two anthracycline class drugs (zorubicin and aclarubicin) and a food dye (E 155) were predicted to be potent inhibitors of RBD – receptor interaction. Results of present study provide evidence for the potential of these compounds asprophylactic medications or for use to reduce disease severity of COVID -19.

Fasting, a practice with historical roots in various cultures, has recently garnered significant interest in the field of medicine. In this article, we delve into the mechanisms underlying fasting-induced autophagy and its therapeutic applications for spike protein associated pathology. We explore the therapeutic potential of fasting on spike protein-related pathology and the role of interventions to upregulate autophagy, including compounds like spermidine, resveratrol, rapamycin, and metformin. In conclusion, fasting, coupled with an understanding of its nuances, holds promise as a therapeutic intervention for spike protein related diseases; with broad implications for human health. This review presents the therapeutic possibility of using autophagy to treat spike protein related diseases, and details the interventions to deploy this therapeutic modality.

Background: Covid-19 was first reported in Wuhan, China in Dec 2019. Since then, it has been transmitted rapidly in China and the rest of the world. While Covid-19 transmission rate has been declining in China, it is increasing exponentially in Europe and America. Although there are numerous studies examining Covid-19 infection, including an archived paper looking into the meteorological effect, the role of outdoor air pollution has yet to be explored rigorously. It has been shown that air pollution will weaken the immune system, and increase the rate of respiratory virus infection. We postulate that outdoor air pollution concentrations will have a negative effect on Covid-19 infections in China, whilst lockdowns, characterized by strong social distancing and home isolation measures, will help to moderate such negative effect. Methods: We will collect the number of daily confirmed Covid-19 cases in 31 provincial capital cities in China during the period of 1 Dec 2019 to 20 Mar 2020 (from a popular Chinese online platform which aggregates all cases reported by the Chinese national/provincial health authorities). We will also collect daily air pollution and meteorology data at the city-level (from the Chinese National Environmental Monitoring Center and the US National Climatic Data Center), daily inter-city migration flows and intra-city movements (from Baidu). City-level demographics including age distribution and gender, education, and median household income can be obtained from the statistical yearbooks. City-level co-morbidity indicators including rates of chronic disease and co-infection can be obtained from related research articles. A regression model is developed to model the relationship between the infection rate of Covid-19 (number of confirmed cases/population at the city level) and outdoor air pollution at the city level, after taking into account confounding factors such as meteorology, inter- and intra-city movements, demographics, and co-morbidity and co-infection rates. In particular, we shall study how air pollution affects infection rates across different cities, including Wuhan. Our model will also study air pollution would affect infection rates in Wuhan before and after the lockdown. Expected findings: We expect there be a correlation between Covid-19 infection rate and outdoor air pollution. We also expect that reduced intra-city movement after the lockdowns in Wuhan and the rest of China will play an important role in reducing the infection rate. Interpretation: Infection rate is growing exponentially in major cities worldwide. We expect Covid-19 infection rate is related to the air pollution concentration, and is strongly dependent on inter- and intra-city movements. To reduce the infection rate, the international community may deploy effective air pollution reduction plans and social distancing policies.

SARS-CoV-2 (CoV-2) is a coronavirus which is causing the actual COVID-19 pandemic. The disease caused by 2019 new coronavirus (2019-nCoV) was named coronavirus disease-19 (COVID-19) by the World Health Organization in February 2020. Primary non-specific reported symptoms of 2019-nCoV infection at the prodromal phase are malaise, fever, and dry cough. The most commonly reported signs and symptoms are fever (98%), cough (76%), dyspnea (55%), and myalgia or fatigue (44%). Nonetheless, recent reports suggest an association between COVID-19 and altered olfactory and taste functions, although smell seems to be more affected than taste. These associations of smell and taste dysfunctions and CoV-2 are consistent with case reports describing a patient with SARS with long term anosmia after recovery from respiratory distress, with the observation that olfactory function is commonly altered after infection with endemic coronaviruses, and with data demonstrating that intentional experimental infection of humans with CoV-299 raises the thresholds at which odors can be detected. Post-viral anosmia and is one of the leading causes of loss of sense of smell in adults, accounting for up to 40% cases of anosmia. Viruses that give rise to the common cold are well known to cause post-infectious loss, and over 200 different viruses are known to cause upper respiratory tract infections. I reviewed the possible mechanisms of smell and taste loss in COVID-19. I concluded that since the existence of such a relationship is likely, it is highly recommended that those patients who experience complications such as smell and/or taste loss, even as unique symptoms, should be considered as potential SARS-CoV-2 virus carriers.

The outbreak of 2019-novel coronavirus (SARS-CoV-2) that causes severe respiratory infection (COVID-19) has spread in China, and the world health organization declared it pandemic. However, no approved drug or vaccines are available, and treatment is mainly supportive and through a few repurposed drugs. In this urgency situation, development of SARS-CoV-2 based vaccines is immediately required. Immunoinformatic and molecular modelling are generally used time-efficient methods to accelerate the discovery and design of the candidate peptides for vaccine development. In recent years, the use of multiepitope vaccines is proved to be a promising immunization strategy against viruses and pathogens, which induce more comprehensive protective immunity. The current study demonstrated a comprehensive in-silico strategy to design stable multiepitope vaccine construct (MVC) from B-cell and T-cell epitopes of essential SARS-CoV-2 proteins with the help of adjuvants and linkers. The integrated molecular dynamics simulations analysis revealed the stability of MVC and its interaction with human Toll-like receptors (TLRs), which trigger an innate and adaptive immune response. Later, the in-silico cloning in a known pET28a vector system also estimated the possibility of MVC expression in E. Coli. Despite this study lacks validation of this vaccine construct in terms of its efficacy, the current integrated strategy encompasses the initial multiple epitope vaccine design concepts. After validation, this MVC can present to be a better prophylactic solution against COVID-19.

Global differences in changes in the numbers of population-adjusted daily test-positive cases (NPDP) and deaths (NPDD) by COVID-19 were analyzed for 49 countries, including developed and developing countries. The changes as a proportion of national population were compared, adjusting by the beginning of test-positive cases increase (BPI) or deaths increase (BDI). Remarkable regional differences of more than 100 fold in NPDP and NPDD were observed. The trajectories of NPDD after BDI increased exponentially within 20 days in most countries. Machine learning analysis suggested that NPDD on 30 days after BDI was the highest in developed Western countries (1180 persons per hundred million), followed by countries in the Middle East (128), Latin America (97), and Asia (7). Furthermore, in Western countries with positive rates of the PCR test of less than 7.0%, the increase in NPDP was slowing-down two weeks after BPI, and subsequent NPDD was only 15% compared with those with higher positive rates, which suggested that the situation of testing might have affected the velocity of COVID-19 spread. The causes behind remarkable differences between regions possibly include genetic factors of inhabitants because distributions of the race and of the observed infection increasing rates were in good agreement globally.

SARS-CoV-2, the novel coronavirus behind COVID-19 pandemic is acquiring new mutations in its genome. Although some mutations provide benefits to the virus against human immune response, a number of them may result in their reduced pathogenicity and virulence. By analyzing more than 3000 high-coverage, complete genome sequences deposited in the GISAID database, here I report a unique 28881-28883:GGG>AAC trinucleotide-bloc mutation in the SARS-CoV-2 genome that results in two sub-strains, described here as SARS-CoV-2g (28881-28883:GGG genotype) and SARS-CoV-2a (28881-28883:AAC genotype). Computational analysis and literature review suggest that this bloc mutation would bring 203-204:RG(arginine-glycine)>KR(lysine-arginine) amino acid changes in the nucleocapsid (N) protein affecting the SR (serine-arginine)-rich motif of the protein, a critical region for the transcription of viral RNA and replication of the virus. Thus, 28881-28883:GGG>AAC bloc-mutation is expected to modulate the pathogenicity of the SARS-CoV-2. Remarkably, SARS-CoV-2g and SARS-CoV-2a strains can be linked with the heterogeneity of COVID-19 cases across different regions within and between countries by analyzing existing data. Sequence analysis suggests that severely affected cities, such as Milan, Lombardy, New York, Paris have the predominant presence of SARS-CoV-2g strains, whereas less affected places like Abruzzo, Lyon, Valencia have a relatively higher presence of SARS-CoV-2a, an indication that the latter strain may contribute to the reduced cases of COVID-19. A similar relationship is observed when Netherlands, Portugal are compared with Spain, France and Germany. These analyses suggest that the SARS-CoV-2 has already evolved into a less infective SARS-CoV-2a affecting COVID-19 cases in different regions. The time a country or region needs to acquire SARS-CoV-2a strains may be indicative to the time it would need to overcome the peak of the COVID-19 cases. To confirm these assumptions, prompt retrospective and prospective epidemiological studies should be conducted in different countries to understand the course of pathogenicity of the SARS-CoV-2a and SARS-CoV-2g. Potential drugs can be designed targeting 28881-28883 region of the N protein to modulate virus pathogenicity.

The issues mothers face in the academy have been discussed for decades. Routinely, new studies report significant differences between women and men at comparable career stages with respect to salary, service demands, publications, grant submissions, and overall funding rates. The COVID-19 pandemic is further exposing these inequalities as women scientists who are parenting while also engaging in a combination of academic related duties are falling further behind. COVID-19 is shaking the very foundations of our society and laying bare the many inequalities that defined our pre-COVID world. We can solve these inequities by investing strategically in creative solutions, thereby making the most of women’s contributions to scientific endeavors. Here we describe strategies that would make the academy more equitable for working mothers now and into the future. Importantly, while the data are clear that mothers are being disproportionally impacted by COVID-19, many groups could benefit from these same ideas. Now is the time to act. Rather than rebuilding what we once knew, let us be the architects of a new world.

COVID-19 is now a major global health crisis, can lead to severe food crisis unless proper measures are not taken. Though a number of scientific studies have addressed the possible impacts of COVID-19 in Bangladesh on variety of issues, problems and food crises associated with aquatic resources and communities are missing. Therefore, this study aimed at bridging the gap in the existing situation and challenges of COVID-19 by linking its impact on aquatic food sector and small-scale fisheries with dependent population. The study was conducted based on secondary data analysis and primary fieldwork. Secondary data focused on COVID-19 overview and number of confirmed, recovered and death cases in Bangladesh; at the same time its connection with small-scale fisheries, aquatic food production, demand and supply was analyzed. Community perceptions were elicited to present how the changes felt and how they affected aquatic food system and small-scale fisheries and found devastating impact. Sudden illness, reduced income, complication to start production and input collection, labor crisis, transportation abstraction, complexity in food supply, weak value chain, low consumer demand, rising commodity prices, creditor’s pressure were identified as the primary affecting drivers. Dependent people felt the measures taken by the Government should be based on protecting the health and food security, although it could be detrimental to economic growth in the short term. The study provides insight into policies adopted by the policy makers to mitigate the effects of the pandemic on aquatic food sector and small-scale fisheries.

During the period of health emergency linked to the current COVID-19 pandemic, the management of children's oral health presents specific problems related to the infectious spread of the disease. These problems must be faced on the one hand by acting on the oral health prevention methods, and on the other by implementing specific protocols relating both to the conditions of oral pathologies that normally do not represent an emergency, and to those clinical situations that fall into the category of pediatric dental emergencies. In this perspective, in addition to defining rigorous and highly effective infection control protocols in the dental settings, it is of fundamental importance to work on remote communication and education aimed at maintaining the oral health of the children. This article, after an analysis of the risk factors from COVID-19 associated with pediatric dental treatment, presents a series of considerations on potential oral prevention strategies and on the management of emergency and non-emergency dental procedures in a context of disease transmission control, proposing new approaches and models of treatment based also on remote interaction techniques which will then retain their usefulness even at the end of the current emergency period.

Recent clinical SARS-CoV-2 studies link diabetes, cardiovascular disease, and hypertension to increased disease severity. In the US, racial and ethnic minorities and low socioeconomic status (SES) individuals are more likely to have increased rates of these comorbidities, lower baseline health, limited access to care, increased perceived discrimination, and limited resources, all of which increase their vulnerability to severe disease and poor health outcomes from SARS-CoV-2. Previous studies demonstrated the disproportionate impact of pandemic and seasonal influenza on these populations, due to these risk factors. This paper reviews increased health risks and documented health disparities of racial and ethnic minorities and low SES individuals in the US. Pandemic response must prioritize these marginalized communities to minimize the negative, disproportionate impacts of SARS-CoV-2 on them and manage spread throughout the entire population. This paper concludes with recommendations applicable to healthcare facilities and public officials at various government levels.

The COVID-19 outbreak has focused attention on the use of social distancing as the primary defence against community infection, yet forcing social animals to maintain that physical distance has presented significant challenges for health authorities and law enforcement. Anecdotal media reports suggest widespread dissatisfaction with social distancing as a policy, yet there is little prior work aimed at measuring community acceptance of social distancing. In this paper, we propose a new approach to measuring attitudes towards social distancing by using social media and sentiment analysis. Over a 4 month period, we found 82.5% of tweets were in favour of social distancing. The results indicate a widespread acceptance of social distancing in the community. We conclude by examining options for estimating the optimal (minimal) social distance required at scale, and the implications for securing widespread community support and acceptance of public health messaging.

Thermal sterilization is generally avoided for 3-D printed components because of the relatively low deformation temperatures for common thermoplastics used for material extrusion-based additive manufacturing. 3-D printing materials required for high-temperature heat sterilizable components for COVID-19 and other applications demands 3-D printers with heated beds, hot ends that can reach higher temperatures than polytetrafluoroethylene (PTFE) hot ends and heated chambers to avoid part warping and delamination. There are several high temperature printers on the market, but their high costs make them inaccessible for full home-based distributed manufacturing required during pandemic lockdowns. To allow for all these requirements to be met for under $1,000, the Cerberus – an open source three-headed self-replicating rapid prototyper (RepRap) was designed and tested with the following capabilities: i) 200^oC-capable heated bed, ii) 500^oC-capabel hot end, iii) isolated heated chamber with 1kW space heater core and iv) mains voltage chamber and bed heating for rapid start. The Cereberus successfully prints polyetherketoneketone (PEKK) and polyetherimide (PEI, ULTEM) with tensile strengths of 77.5 and 80.5 MPa, respectively. As a case study, open source face masks were 3-D printed in PEKK and shown not to warp upon widely home-accessible oven-based sterilization.

A novel coronavirus (SARS-CoV-2), causing an emerging coronavirus disease (COVID-19), first detected in Wuhan City, Hubei Province, China has resulted in an outbreak in China which has taken a catastrophic turn with high toll rates in China and subsequently spreading across the globe. The rapid spread of this virus to more than 175 countries while affecting nearly 500,000 persons and causing more than 22,000 human deaths, it has resulted in a pandemic situation in the world. The SARS-CoV-2 virus belongs to the genus Betacoronavirus, like MERS-CoV and SARS-CoV, all of which originated in bats. It is highly contagious, causing symptoms like fever, dyspnea, asthenia and pneumonia, thrombocytopenia and the severely infected patients succumb to the disease. Coronaviruses (CoVs) among all known RNA viruses have the largest genomes ranging from 26 to 32 kb in length. Extensive research has been conducted to understand the molecular basis of the SARS-CoV-2 infection and evolution, develop effective therapeutics, antiviral drugs and vaccines, and to design rapid and confirmatory viral diagnostics as well as adopt appropriate prevention and control strategies. Till date, no clinically proclaimed, proven therapeutic antibodies or specific drugs and therapeutics, and vaccines have turned up. Several molecular diagnostic tests such as Real Time-PCR, isothermal loop-mediated amplification of coronavirus (i-LACO), full genome analysis by next-generation sequencing (NGS), multiplex nucleic acid amplification, and microarray-based assays are in use currently for the laboratory confirmation of this CoV infection. In this review article, we describe the basic molecular organization and phylogenetic analysis of the coronaviruses, including the SARS-CoV-2, and recent advances in diagnosis and vaccine development in brief and focusing mainly on developing potential therapeutic options that can be explored to manage this pandemic virus infection, which would help in valid countering of COVID-19.

Africa is gradually becoming an epicentre for the COVID-19 pandemic. From the current trends of the disease, Africa might be the last hardest hit continent. While scientific investigations are ongoing to develop effective management through medications and vaccines, existing knowledge, perceptions and attitudes could be harnessed to develop an effective strategy to curb community transmission of the COVID-19. The present study assessed the awareness level, perceptions and attitudes of people living in rural, peri-urban and urban communities in Northern Ghana and their preparedness for the prevention and containment of COVID-19. We conducted a face-to-face interview and administered 553 semi-structured questionnaires in eighteen (18) rural and peri-urban/urban communities under Tolon District, Kumbungu Districts, Sagnarigu Municipality, Savelugu Municipality and Tamale Metropolis from 23^rd of April to 8^th of June 2020. The percentage of male to female among the respondents was 56.8% and 43.2%, respectively. Nearly half (41%) of the respondents had no formal education and 91.3% of them were Muslims. Most of the respondents (85%) held the view that COVID-19 is a punishment from God. There was a significant difference (P<0.05) between the time rural and peri-urban/urban communities first heard of COVID-19. Majority (63%) of the rural respondents depended on radio, while the peri-urban/urban respondents (51%) relied on television for information on COVID-19. All respondents were aware of COVID-19 and 91.7% could mention at least two symptoms of the disease but 18% believed there was no COVID-19 in Ghana. Most of the respondents (69.6%) believed they will not contract the virus. Our findings may provide useful data to government and other stakeholders in the COVID-19 fight.

This study aimed to focus on how to design a low-cost greenhouse for the cultivation of crops, to propose the cost-effectiveness analysis of small agribusiness, and to promote sustainable agricultural production during and after the COVID-19 crisis for helping grassroots and anyone who lost their job. This article is qualitative engineering research, studying of literature reviews of greenhouse farming concept and Micro, Small and Medium Enterprises, then, designing low-cost greenhouse model which was preliminarily adapted for hot climate countries. Three plants that were selected as representative plants of this model include sunflower, water spinach, and wheat. The greenhouse model, measuring 5 x 7 x 4 m (W x L x H), was designed for this mission. The total cost of one building is approximately 97,994 THB. For the worthiness of the investment, farmers should build at least three greenhouse buildings, which will return total income to farmers approximately 34,666.09 THB per month. The suggestion includes further knowledge and financial supports from the government sectors among farmers, then, boost them up using high-level technology and also planting high-price agribusiness production to promote the local economy to be strong and sustainable.

Coronavirus Disease 2019 (COVID-19), caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome - Coronavirus-2) of the family Coronaviridae, appeared in Wuhan, Hubei province, China being its epicenter in December 2019. This disease was declared as posing Public Health International Emergency by World Health Organization on January 30, 2020, attained the status of a very high-risk category on February 29, and now having a pandemic status (March 11, 2020). COVID-19 has presently spread to more than 195 countries/territories while killing nearly 19,600 humans out of cumulative confirmed cases accounting to more than 430,000 within a short period of just a few weeks. The majority of deaths have been reported in Italy and China. Researchers worldwide are pacing with high efforts to counter the spread of this virus and to design effective vaccines and therapeutics/drugs. Few of the studies have shown the potential of animal-human interface and zoonotic links in the origin of SARS-CoV-2. Exploring the possible zoonosis and revealing the factors responsible for its initial transmission from animals to humans will pave ways to design and implement effective preventive and control strategies to counter COVID-19. The present review presents an overview of COVID-19 and the causative virus SARS-CoV-2, with particular emphasis on the role of animals and their jumping the cross-species barriers, experiences learned from SARS- and MERS-CoVs, zoonotic links, and spillover events, transmission to humans and rapid spread., highlighting in very brief the preventive and control measures along with a few of the recent research developments to counter this pandemic virus/disease.

Covid-19 is a new coronavirus disease first described in December 2019. This respiratory illness is severe and potentially fatal. Severe cases make up to 15%, lethality ranges between 1.5 and more than 10 %. What is urgently needed is an efficient pharmacological treatment for the treatment of severe cases. During the infection of alveolar epithelial cells of the lung, the ACE2 receptor has a central function. The antimalarial drugs chloroquine phosphate (CQ) and hydroxychloroquine (HCQ) impair in vitro the terminal glycosylation of ACE2 without significant change of cell-surface ACE2 and, therefore, might be potent inhibitors of SARS-CoV-2 infections. Starting inhibition at 0.1 µM, CQ completely prevented in vitro infections at 10 µM, suggesting a prophylactic effect and preventing the virus spread 5 hours after infection. In a first clinical trial, CQ was effective in inhibiting exacerbation of pneumonia, improving lung imaging findings, promotion of virus-negative conversion, and shortening the disease. In addition, HCQ, which is three times more potent than CQ in SARS-CoV-2 infected cells (EC50 0.72 µM), was significantly associated with viral load reduction/disappearance in COVID-19 patients compared to controls. Theoretically, CQ and HCQ could thus be effectively used in the treatment of SARS-CoV pneumonia. From a pharmacological standpoint, however, the major problems of oral treatment with these drugs are possible severe side effects and toxicity. Concretely, this relates to (a) the inconsistent individual bioavailability of these drugs at the alveolar target cells, depending on intestinal resorption, hepatic first-pass metabolism and accumulation in liver, spleen and lung, and (b) the need for a relatively high concentration of 1-5 µM at the alveolar surface. Therefore, we propose in a first dose estimation the use of HCQ as an aerosol in a dosage of 2-4 mg per inhalation in order to reach sufficient therapeutic levels at the alveolar epithelial cells. By using a low-dose non-systemic aerosol, adverse drug reactions will markedly be reduced compared with oral application. This increase in tolerability enables a broader use for prevention and after contact with an infected person, which would be an advantage especially for the high-risk, often multi-morbid and elderly patients. Empirical data on self-medication with a one-week aerosol application by two of the authors is presented. Inhalation was well tolerated without relevant side effects.

The COVID-19 pandemic has obliged Governments all around the world to take confinement and social 13 distancing measures. The reduction of leisure and production activities on beaches and ports have 14 disappeared direct and indirect contamination such as plastics, hydrocarbon spill, microbiological loads, 15 noise level, etc. leading to temporary improved environmental conditions, converting the beaches 16 similar to Marine Protected Areas. Some conditions are briefly analyzed through local surveys and in situ 17 observations in the popular beaches and ports of Salinas, Manta and Galápagos. 97-99 % of surveyed 18 people agreed that beaches have notoriously improved during confinement at least from visual 19 observation. On a scale from 1 (worst) to 5 (best), the beaches were rated 2.23 and 2.83 (less than 20 acceptable) before quarantine, and 4.48 and 4.33 after it for Salinas and Manta respectively. The 21 beaches have less garbage in general and plastic, even though there has been an increase in plastic and 22 face mask production around the world. In Salinas, 72%, and 23 % of surveyed people have seen small 23 pelagic fish, whilst in Manta 75%, and 41% of people saw the same, but also 17% of people have seen 24 whales (humpback and shark-whales) and dolphins practically swimming on the beach. Manta rays, 25 turtles, and other types of species were also observed. In Galapagos beaches, turtles have been 26 observed many more times than usual. The main plausible reason is the decrease in noise level. It is 27 recommended to take this unique opportunity, to construct a baseline data and information on physical, 28 chemical, biological, microbiological coastal oceanographic science, and from them to establish a proper 29 Coastal Zone Management based on beach description, water, and beach quality, human dimension, 30 and economic value indexes. This data and information construction should ideally be done before the 31 beaches are open.

COVID-19 is the first known coronavirus pandemic. Nevertheless, the seasonal circulation of the four milder coronaviruses of humans – OC43, NL63, 229E and HKU1 – raises the possibility that these viruses are the descendants of more ancient coronavirus pandemics. This proposal arises by analogy to the observed descent of seasonal influenza subtypes H2N2 (now extinct), H3N2 and H1H1 from the pandemic strains of 1957, 1968 and 2009, respectively. Recent historical revisionist speculation has focussed on the influenza pandemic of 1889-1892, based on molecular phylogenetic reconstructions that show the emergence of human coronavirus OC43 around that time, probably by zoonosis from cattle. If the “Russian influenza”, as The Times named it in early 1890, was not influenza but caused by a coronavirus, the origins of the other three milder human coronaviruses may also have left a residue of clinical evidence in the 19th century medical literature and popular press. In this paper, we search digitised 19th century British newspapers for evidence of previously unsuspected coronavirus pandemics. We conclude that there is little or no corpus linguistic signal in the UK national press for large-scale outbreaks of unidentified respiratory disease for the period 1785 to 1890.

Convalescent blood product therapy has been introduced since early 1900s to treat emerging infectious disease based on the evidence that polyclonal neutralizing antibodies can reduce duration of viremia. Recent large outbreaks of viral diseases for whom effective antivirals or vaccines are still lacking has revamped the interest in convalescent plasma as life-saving treatments. This review summarizes historical settings of application, and surveys current technologies for collection, manufacturing, pathogen inactivation, and banking, with a focus on COVID-19.

An intense scientific debate is ongoing as to the origin of SARS-CoV-2. An oft-cited piece of information in this debate is the genome sequence of a bat coronavirus strain referred to as RaTG13 1 mentioned in a recent Nature paper 2 showing 96.2% genome homology with SARS-CoV-2. This is discussed as a fossil record of a strain whose current existence is unknown. The said strain is conjectured by many to have been part of the ancestral pool from which SARS-CoV-2 may have evolved 7, 8, 9. Multiple groups have been discussing the features of the genome sequence of the said strain. In this paper, we report that the currently specified level of details are grossly insufficient to draw inferences about the origin of SARS-CoV-2. De-novo assembly, KRONA analysis for metagenomic and re-examining data quality highlights the key issues with the RaTG13 genome and the need for a dispassionate review of this data. This work is a call to action for the scientific community to better collate scientific evidence about the origins of SARS-CoV-2 so that future incidence of such pandemics may be effectively mitigated.

The COVID-19 pandemic changed the world of medical education, moving it years ahead of time into the future. Many concepts needed to be changed, so did the methodologies. Nevertheless, clinical assessment remained tricky. This work highlights the outcome of the work of College of Medicine and Medical Sciences at the Arabian Gulf University in Bahrain in performing virtual clinical examination using Zoom™. Tips in this article are meant to help plan, implement and evaluate clinical assessments virtually.

The world is currently experiencing COVID-19, one of the worst pandemics that have happened in this century, affecting 10.7 million people worldwide. It has caused massive growth in the number of employees working from home. However, employees have minimal cybersecurity resources unlike organizations with security teams protecting them against attacks. Hence, cybersecurity plays an important role as users can be easily targeted by cybercriminals. This paper examines how cyberattacks have increased during this pandemic and shows how greatly they have affected health organizations, individuals and social networking applications. Results of the attacks include data breaches, false announcements and operations being disrupted. Attacks occurring during this pandemic and how they were handled are also critically discussed. The existing contributions do touch on related attacks but do not provide in-depth solutions regarding the issues. Even though there are many works and findings that were done previously, technology is ever evolving. Therefore, we need to be well versed with current and future issues and provide the latest mechanisms to prevent cybersecurity threats from occurring. On our share, we intend to present our findings on the challenges being faced by the population and its increasing threats as well as presenting unique solutions that can help organizations or related persons understand or spread awareness on the importance of cybersecurity. Through the research performed in this paper, it is found that there are many ways these issues can be alleviated. However, the issue is that there is significant lack of action and investment in terms of actual implementation and application of the available solutions.

Utility of vaccine campaigns to control coronavirus disease 2019 (COVID-19) is not merely dependent on vaccine efficacy and safety. Vaccine acceptance among the general public and the healthcare workers, appears to have a decisive role for successful control of the pandemic. The aim of this review was to provide an up-to-date assessment of COVID-19 vaccination acceptance rates worldwide. A systematic search of the peer-reviewed English survey literature indexed in PubMed was done on December 25, 2020. Results from 30 studies, met the inclusion criteria and formed the basis for final COVID-19 vaccine acceptance estimates. Results of an additional recent survey from Jordan and Kuwait was considered in this review as well. Survey studies on COVID-19 vaccine acceptance rates were found from 33 different countries. Among adults representing the general public, the highest COVID-19 vaccine acceptance rates were found in Ecuador (97.0%), Malaysia (94.3%), Indonesia (93.3%) and China (91.3%). On the other hand, the lowest COVID-19 vaccine acceptance rates were found in Kuwait (23.6%), Jordan (28.4%), Italy (53.7), Russia (54.9%), Poland (56.3%), US (56.9%), and France (58.9%). Only eight surveys among healthcare workers (doctors, nurses) were found, with vaccine acceptance rates ranging from 27.7% in the Democratic Republic of the Congo to 78.1% in Israel. In a majority of survey studies among the general public (62%), the acceptance of COVID-19 vaccination showed a level of ≥ 70%. Low rates of COVID-19 vaccine acceptance were reported in the Middle East, Russia, Africa and several European countries. This could represent a major problem in the global efforts that aim to control the current COVID-19 pandemic. More studies are recommended to address the scope of COVID-19 vaccine hesitancy. Such studies are particularly needed in the Middle East Africa, Eastern Europe, Central Asia, Middle and Latin America.

The pharmacology of azithromycin, and the actions of certain bee products, suggest the possibility of overlap with the pathophysiology of COVID-19 at several points in the disease process. First, intercellular epithelial tight junctions of the respiratory tract serve as a critical barrier to invaders. Pathophysiological factors capable of disrupting this epithelial barrier include viral virulence factors such as those observed for other coronaviruses; virulence factors derived from potentially synergistic pathogens such as Candida albicans and Porphyramonas gingivalis; and imbalances in the host inflammatory response. Azithromycin, and to a lesser extent, certain bee products, appear to have actions that oppose such processes. Second, the matrikine PGP or its derivatives may contribute to risk in individuals at high risk for serious COVID-19 infection, especially during reactivation; but azithromycin is capable of modulating PGP in some contexts. Third, the most serious COVID-19 infections are associated with massive upregulation of inflammatory cytokines such as IL-6, TNF alpha, and other inflammatory cytokines. The anti inflammatory actions of azithromycin and bee derived products such as melittin are potentially capable of modulating these processes, as well. Azithromycin is already in current use as a treatment for COVID-19; however, it's utility as a protector of epithelial barrier function would be most likely to be realized in prophylactic context rather than in a treatment context. Similarly, since the anti inflammatory effects of bee products take time, their effectiveness of melittin and other bee products would be expected to be maximized in a prophylactic context. In the context of the current pandemic, prophylaxis with azithromycin, bee products, or both, might be warranted for individuals at high risk for serious COVID-19 infection.

Abstract: A primary action of vitamin D is regulation of gene transcription. Many cell types possess genes that make antimicrobial peptides (AMPS) (endogenous antibiotics), recently discovered to be regulated by vitamin D. Two examples are cathelicidin and beta defensins, both bioactive against many different bacteria, fungi, mycobacteria, parasites and viruses. The signal transduction pathway is triggered by sensing microorganisms via cell surface receptors, causing intracellular production of calcitriol (1,25(OH)2D) and vitamin D receptors, leading to upregulation of AMP production. Serum 25(OH)D concentrations required to sustain adequate AMP production to eradicate infections are unknown. Vitamin D3 is photosynthesized in skin in amounts ranging from 10,000 (250 mcg) to 25,000 (625 mcg) International Units (IU) from 7-dehydrocholesterol after whole-body exposure to one minimal erythemal dose (MED) of ultraviolet B (UVB) radiation, and is impacted by many factors including geographic localities, seasonal changes and skin pigmentation. We and others have reported extended daily oral dosing with these amounts of vitamin D3 safe. We routinely observe serum 25(OH)D concentrations below 20ng/ml on new admissions, which have been reported insufficient to sustain AMP production. In contrast serum 25(OH)D concentrations above 100ng/ml have been reported after serial UVB treatments for psoriasis. Little vitamin D naturally occurs in food, and insufficient sun exposure may be causing worldwide deficiency. We review evidence suggesting that higher daily intakes of vitamin D3 than the currently recommended 600 (15 mcg) IU/day may be necessary to sustain AMP production in the face of an overwhelming infection, particularly in non-Hispanic blacks, a high risk population suffering the worst outcomes from COVID-19. We propose that increased vitamin D supplementation could provide a safe and cost-effective way to protect all populations from infections, in particular those from pandemic COVID-19.