SARS-CoV-2 is a novel and highly pathogenic coronavirus, which was first diagnosed in Wuhan city, China, in 2019, and spread to 185 countries and territories, and as of April 29, 2020, more than 3.11 million cases were recorded, and more than 217,000 people were killed. Despite all worldwide efforts, there is currently no vaccine, any drugs available to protect people against deadly SARS-CoV-2 coronavirus. The world urgently needs a SARS-CoV-2 coronavirus vaccine or effective antiviral drugs to relieve the human suffering associated with the pandemic that kills thousands of people every day. The SARS-CoV-2 genome encode a non-structural proteins named as ORF1a/b, and structural proteins such as spike (S) glycoprotein, nucleocapsid protein (N), small envelop protein (E) and matrix protein (M). A number of studies have been shown that CoV spike (S) glycoprotein and nucleocapsid protein (N) could be promising targets for vaccine, antibodies and therapeutic drug development to combat with deadly, pandemic SARS-CoV-2. Purposes of the present paper is the sequence analysis and amino acid variations of structural proteins deduced from novel coronavirus SARS-CoV-2 strains, isolated in different countries. Multiple sequence alignment of S, N and E proteins from four different coronavirus species, are also described. It is expected that the data from these studies will be very useful for the the designing and development of vaccines, antibodies and therapeutic agents that can be used to combat with the highly pathogenic SARS-CoV-2 coronavirus worldwide.

We describe a 90-year-old male presenting with disequilibrium, loss of balance and difficulty walking for three days prior to initial presentation. Interestingly, he denied cough, fever or dyspnea prior to arrival. Over the course of 48 hours, the patient developed acute respiratory distress syndrome (ARDS) requiring intubation, diagnosed with COVID-19 infection and was treated in the intensive care unit where he died. Since the initial cases in Wuhan China in Dec 2019, the medical and epidemiological communities have learned much about the presenting features, symptomatology, epidemiology, transmission and common physical, laboratory and radiological findings of this disease. Although common symptoms are already established, it is very important to learn and record atypical symptoms or presentations of this highly contagious disease. By doing so, we will be able to recognize earlier atypical symptoms and prevent the environmental exposure to Health care workers and future patients as well. We report that Central disequilibrium may be such as initial presenting sign and symptom of impending respiratory failure from SARS-CoV-2 virus. These atypical findings such as presyncope may precede common respiratory complications of SARS-CoV-2.

In December 2019, outbreak of novel coronavirus (COVID-19) occurred in Wuhan, Hubei Province, China and exported across the world leading to thousands of deaths and millions of suspected cases. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection into the host undergoes a huge number of complex replicative machineries which still remains unclear. Understanding the mechanism (s) of replication and mode of infection of SARS-CoV2 to human cells will help us in the development of novel vaccines or drugs for the eradication and prevention of the disease. This review compiles the knowledge of SARS-CoV2 replicative machinery, mode of infection to the human cells and the development of drugs and vaccines which are currently under clinical trials.

Increasing evidence points to host Th17 inflammatory responses as contributing to the severe lung pathology and mortality of lower respiratory tract infections from coronaviruses. This includes host inflammatory and cytokine responses to COVID-19 caused by the SARS-2 coronavirus (SARS CoV2). From studies conducted in laboratory animals, there are additional concerns about immune enhancement and the role of potential host immunopathology resulting from experimental human COVID-19 vaccines. Here we summarize evidence suggesting there may be partial overlap between the underlying immunopathologic processes linked to both coronavirus infection and vaccination, and a role for Th17 in immune enhancement and eosinophilic pulmonary immunopathology. Such findings help explain the link between viral-vectored coronavirus vaccines and immune enhancement and its reduction through alum adjuvants. Additional research may also clarify links between COVID-19 pulmonary immunopathology and heart disease.

The recent outbreak of novel coronavirus (SARS-CoV-2 or 2019-nCoV) and its spread to the whole world is currently posing one of the major threats to human health and the world economy. It has been suggested that SARS-CoV-2 is similar to SARS-CoV based on the genome sequence comparison. Despite the genomic similarity between SARS-CoV and SARS-CoV-2, the spike glycoprotein and receptor binding domain in SARS-CoV-2 shows considerable difference compared to SARS-CoV, due to the presence of several point mutations. We analyzed the receptor binding domain (RBD) from recently published 3D structure of spike glycoprotein of SARS-CoV-2 and compared with RBD of SARS-CoV. The observations highlight few important features of RBD in the light of the recently published findings from the 3D structures of spike glycoprotein and its complex with human angiotensin-converting enzyme 2 (ACE2) (Yan, R., et al. (2020); Wrapp, D., et al. (2020); Walls, A. C., et al. (2020)).

In this report, we demonstrate that it is possible to design epitope-based peptide vaccine candidates to counteract the novel China coronavirus (2019-nCoV) by using an approach similar to the one used in cancer neoantigen vaccination therapy. We identified multiepitope peptide vaccine candidates against 2019-nCov that can potentially trigger both CD4⁺ and CD8⁺ T cell immune response with increased efficiency due to the presence of CD4⁺ and CD8⁺ T cell epitopes and a cathepsin-sensitive linker. Furthermore, we suggest that the peptide design strategy should incorporate population-specific HLA alleles in order to optimize binding specificity of the peptides. We refer to this as populationalized vaccinomics.

A novel coronavirus called 2019-nCoV was recently found in Wuhan, Hubei Province of China, and now is spreading across China and other parts of the world. 2019-nCoV spreads more rapidly than SARS-CoV. Unfortunately, there is no drug to combat the virus. It is of high significance to develop a drug that can combat the virus effectively before the situation gets worse. It usually takes a much longer time to develop a drug using traditional methods. For 2019-nCoV, it is now better to rely on some alternative methods to develop drugs that can combat such a disease effectively since 2019-nCoV is highly homologous to SARS-CoV. In this paper, we first collected virus RNA sequences from the GISAID database, translated the RNA sequences into protein sequences, and built a protein 3D model using homology modeling. Coronavirus main protease is considered to be a major therapeutic target, thus this paper focused on drug screening based on the modeled 2019-nCov_main_protease structure. The deep learning based method DFCNN, developed by our group, can identify/rank the protein-ligand interactions with relatively high accuracy. DFCNN is capable of performing virtual screening quickly since no docking or molecular dynamic simulation is needed. DFCNN identifies potential drugs for 2019-nCoV protease by performing drug screening against 4 chemical compound databases. Also, we performed drug screening for all tripeptides against the binding site of 2019-nCov_main_protease since peptides often show better stability, more bio-availability and negligible immune responses. In the end, we provided the list of possible chemical ligands and peptide drugs for experimental validation.

The literature is scarce in the evaluation of Behçet’s disease (BD) among individuals during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Then, an epidemiological study was conducted using the data from 46 hospitalized patients with BD and coronavirus disease (COVID)-19 representing a prevalence of 2,11 patients per 100,000 inhabitants. From the study sample, 58.7% (27 patients) were female, and 67.4% (31 patients) were White. The main symptoms were fever (40; 87.0%), cough (38; 82.6%), dyspnea (35; 76.1%), and peripheral saturation below 95% (35%, 76.1%). The need for intensive care unit support occurred for 39.1% (18) patients. Also, 21.7% (10) patients needed invasive ventilatory support and 47.8% (22) needed non-invasive ventilatory support. A total of 73.9% (34) of patients lived, and 26.1% (12) of patients died. Only the presence of respiratory discomfort [37.9% vs. 5.9%] was more common among those who died. Patients with BD were not at an increased risk of worse COVID-19 outcomes in Brazil.

The recently reported microbial natural product N-benzoyl-tryptophane (1) along with twenty-two diverse known bioactive compounds were isolated from the marine Aspergillus terreus LGO13 after its re-cultivation using liquid culture fermentation. Structures of the isolated compounds were established on the basis of HR-ESIMS 1D/2D NMR spectroscopy, and comparison with literature data. The antimicrobial, cytotoxicity, and antiviral activities of the microbial extract and the obtained compounds were investigated using a set of microorganisms, cervix carcinoma KB-3-1, non-small cell lung cancer (NSCLC) A549, and coronavirus (SARS-CoV-2), respectively. Molecular docking (MD) simulation was employed to explore the theoretical targets of the isolated metabolites as anti-SARS-CoV-2 agents. Chaetominine (2) seemed to be a potential candidate against papain-like protease (PLpro), one of the viral proteins being aimed by recent research as a possible target of anti-covid agents. Inspired by the MD results, we accordingly assessed the antiviral efficacy of chaetominine (2), fumitremorgin C (6), and azaspirofuran A (9) against SARS-CoV-2. Fumitremorgin C (6) showed a high selectivity index (SI = 20.3), while chaetominine (2) and azaspirofuran A (9) showed moderate selectivity index (SI = 6.6 and 3.2, respectively). These results showed a promising antiviral activity of Fumitremorgin C against SARS-CoV-2 virus.

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.

A global event such as the COVID-19 crisis presents new, often unexpected responses that are fascinating to investigate from both, scientific and social standpoints. Despite several documented similarities, the Coronavirus pandemic is clearly distinct from the 1918 flu pandemic in terms of our exponentially increased, almost instantaneous ability to access/share information, offering an unprecedented opportunity to visualise rippling effects of global events across space and time. Personal devices provide “big data” on people’s movement, the environment and economic trends, while access to the unprecedented flurry in scientific publications and media posts provides a measure of the response of the educated world to the crisis. Most bibliometric (co-authorship, co-citation, or bibliographic coupling) analyses ignore the time dimension, but COVID-19 has made it possible to perform a detailed temporal investigation into the pandemic. Here, we report a comprehensive network analysis based on more than 20000 published documents on viral epidemics, authored by over 75,000 individuals from 140 nations in the past one year of the crisis. In contrast to the 1918 flu pandemic, access to published data over the past two decades enabled a comparison of publishing trends between the ongoing COVID-19 pandemic and those of the 2003 SARS epidemic, to study changes in thematic foci and societal pressures dictating research over the course of a crisis.

Taking advantage of tourists’ intensive flow, the SARS-CoV-2 virus rapidly spread causing thousands of deaths globally. Trying to contain the already pandemic virus, government travel restrictions were suddenly imposed. Consequently, the tourism industry, which at that moment employed one in ten workers globally, suddenly collapsed. Hundreds of thousands of workers immediately lost their income. Flights were cancelled, and thousands of tourists were stuck abroad with no means to return to their home countries. The gravity of the situation raised the question of whether there was scholarly knowledge that could have helped manage tourism during the current pandemic. To answer this question, a methodical literature review was performed, allowing for up to 900 publications to be analysed. Keywords used were pandemic, tourism, tourist and travel. Based on this process, 63 publications were selected for further analysis. Among these, less than 5% were focused on the tourism side of the problem. As such, this research concludes that, by the time the novel coronavirus emerged, there was, virtually, no scholarly knowledge on how to manage tourism during pandemic times so as to avoid chaos, and that the scholarly community studying related issues is very small. Moving forward, this article recommends that research funding agencies and universities encourage the sound development of this area of knowledge. Aspects that should be investigated include when, how and by whom should tourism be halted, as well as the feasibility of a Tourism World Fund for supporting related costs.

Emerging viruses description have grown at an unprecedented rate since the beginning of the 21^st century. The emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and its related illness, Coronavirus Disease 2019 (COVID-19) has been reported as the third highly pathogenic coronavirus introducing itself into human population in the current era after the SARS-CoV and Middle East Respiratory Syndrome (MERS-CoV). Molecular and cellular studies considering the pathogenesis of this novel coronavirus are still in the early stages of research, however, regarding the similarity of SARS-CoV-2 and other coronaviruses, it could be hypothesized that the NF-κB, Cytokine regulation, ERK, and TNF-α signaling pathways are the more likely causes of inflammation upon onset of COVID-19. There are several drugs prescribed and used to alleviate the activity of these inflammatory cellular signaling pathways which might be beneficial for developing novel therapeutic modalities against COVID-19. In this review, we briefly summarized the alteration of cellular signaling pathways affected by coronavirus infection, particularly SARS-CoV and MERS-CoV and tabulated the current therapeutic agents approved for previous human diseases.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an RNA virus, is responsible for coronavirus disease 2019 (COVID-19) pandemic of 2020. Experimental evidence suggests that microRNA can mediate an intracellular defence mechanism against some RNA viruses. The purpose of this study was to identify microRNA with predicted binding sites in the SARS-CoV-2 genome, compare these to their microRNA expression profiles in lung epithelial tissue and make inference towards possible roles for microRNA in mitigating coronavirus infection. We hypothesize that high expression of specific coronavirus-targeting microRNA in lung epithelia may protect against infection and viral propagation, conversely low expression may confer susceptibility to infection. We have identified 128 human microRNA with potential to target the SARS-CoV-2 genome, most of which have very low expression in lung epithelia. Six of these 128 microRNA are differentially expressed upon in vitro infection of SARS-CoV-2. Twenty-eight and 23 microRNA also target the SARS-CoV and MERS-CoV, respectively. In addition, 48 and 32 microRNA are commonly identified in two other studies. Further research into identifying bona fide coronavirus targeting microRNA will be useful in understanding the importance of microRNA as cellular defence mechanism against pathogenic coronavirus infections.

Seven human coronaviruses are known to infect humans. The most recent one, SARS-CoV-2, was isolated and identified in January 2020 from a patient presenting with severe respiratory illness in Wuhan, China. Even though viral coinfections have the potential to influence the resultant disease pattern in the host, very few studies have looked at the disease outcomes in patients infected with both HIV and hCoVs. Groups are now reporting that even though HIV-positive patients can be infected with hCoVs, the likelihood of developing severe CoV-related diseases in these patients is often similar to what is seen in the general population. This review aimed to summarize the current knowledge of coinfections reported for the HIV and hCoVs. Also, based on the available data, this review aimed to theorize why HIV-positive patients do not frequently develop severe CoV-related diseases.

The biosynthesis of DNA inherently competes with RNA synthesis because it depends on the reduction of ribonucleotides (RNA precursors) to 2’-deoxyribonucleotides by ribonucleotide reductase (RNR). Hence, RNA viruses can increase viral RNA production in cells by partially blocking the synthesis of DNA, e.g. by downregulating the mammalian selenoprotein thioredoxin reductase (TR), which normally acts to sustain DNA synthesis by regenerating reduced thioredoxin, a hydrogen donor for RNR. Computational and preliminary experimental evidence supports the hypothesis that a number of pathogenic RNA viruses, including HIV-1, Ebola, Zika, some flu viruses, and SARS-CoV-2, target TR isoforms by antisense. TR knockdown would create a host antioxidant defect that could be partially rectified by increased selenium intake, or be exacerbated by selenium deficiency, contributing to viral pathogenesis. There are several non-selenium-dependent means that viruses might also exploit to slow DNA synthesis, such as targeting RNR itself, or components of the glutaredoxin system, which serves as a backup redox system for RNR. HIV-1 substantially downregulates glutathione synthesis, so it interferes with both the thioredoxin and glutaredoxin systems. Computational results suggest that, like Ebola, SARS-CoV-2 targets TR3 by antisense. TR3 is the only TR isoform that includes an N-terminal glutaredoxin domain, so antisense knockdown of TR3 may also affect both redox systems, favoring RNA synthesis. In contrast, some DNA viruses encode their own glutaredoxins, thioredoxin-like proteins and even RNR homologues – so they are doing just the opposite, favoring DNA synthesis. This is clear evidence that viruses can benefit from shifting the RNA:DNA balance to their advantage.

This brief note aims to explain the scope in conducting large-scale serological surveys of SARS-CoV-2 to define the landscape of population immunity without overlooking the inherent uncertainty steaming from sampling design and diagnostic validity. The note completes with a succinct statistical appendix of simple methods for estimating prevalence from random population samples using imperfect diagnostic tests.

The outbreak across the globe due to coronavirus disease 2019 (COVID-19) has spread abruptly by infected humans worldwide. The continuous efforts by scientists is on way to understand how pandemic of COVID-19 resembles and differs from serve acute respiratory syndrome coronavirus (SARS-CoV) at transcriptomic and genomic level. The SARS-CoV and COVID-19 exploits the angiotensin converting enzyme 2 (ACE2) receptor to gain entry inside the cells.We analyzed the entry COVID-19 into host cell due to receptor binding domain (RBD) of spike glycoprotein. The proposed simulation data shows similar ternary structures from two viruses shares approximately 80 percent identity in amino acid sequences. Our molecular modeling investigation signifies that angiotensin converting enzyme 2 (ACE2) has stronger interaction with COVID -19 RBD. The Amino acid phenylaniline F486 LOOP plays vital role due to its penetration into hydrophobic pocket in ACE2.The said investigation of S-Glycoprotein RBD of COVID-19 or SARS-CoV-2 via ACE2 provides post genome analysis of protein-protein interaction for rapid assessing transmission of infected patients by deadly CoVID-19. The scientific data extracted implies early guidance to control and viral prevention of CoVID-19.

At the time of reception of this article (April 2, 2020), efforts to develop a specific vaccine against SARS-Cov-2, the causative agent of the coronavirus disease 2019 (COVID-19), had just begun trial phase 1, but full validation of this and other current developments is likely to take many more months to reach completion. The ongoing pandemic constitutes a major health burden of world proportions that is also having a devastating impact on whole economies worldwide, the knock-on effects of which could be catastrophic especially in poorer countries. Alternative measures to ameliorate the impact and hamper or minimally slow down disease progression are urgently called for. This review discusses past and currently evolving data on the etiological agent of the current pandemic, SARS-CoV-2, and its host cell receptors with a view to disclosing alternative drugs for palliative or therapeutic approaches. Firstly, SARS-CoV-2 exhibits marked tropism for cells that harbor the membrane-bound metalloprotease angiotensin-converting enzyme 2 (ACE2) at their plasmalemma, predominantly in cells lining the oral cavity, upper respiratory tract, and bronchoalveolar cells, making these epithelial mucosae the most likely viral receptor cell targets and entry routes. Secondly, the crystal structures of several coronavirus spike proteins in complex with their cell host target receptors, and of SARS-Cov-2 in complex with an inhibitor, are now available at atomic resolution through X-ray diffraction and cryo-electron microscopy studies. Thirdly, viral entry of other viruses has been successfully blocked by inhibiting viral endogenous proteases or clathrin/dynamin-dependent endocytosis, the same internalization pathway followed by ACE2 and some viruses. Fourthly, the target cell-surface receptor molecules and SARS-CoV-2 possess other putative sites for drugs potentially modulating receptor activity or virus processing. A multi-pronged pharmacological approach attacking more than one flank of the viral-receptor interactions is worth considering as a front-line strategy.

The 2019 novel coronavirus (2019-nCoV) causes novel coronavirus pneumonia (NCP). Given that approved drug repurposing becomes a common strategy to quickly find antiviral treatments, a collection of FDA-approved drugs can be powerful resources for new anti-NCP indication discoveries. In addition to synthetic compounds, Chinese Patent Drugs (CPD), also play a key role in the treatment of virus related infections diseases in China. Here we compiled major components from 38 CPDs that are commonly used in the respiratory diseases and docked them against two drug targets, ACE2 receptor and viral main protease. According to our docking screening, 10 antiviral components, including hesperidin, saikosaponin A, rutin, corosolic acid, verbascoside, baicalin, glycyrrhizin, mulberroside A, cynaroside, and bilirubin, can directly bind to both host cell target ACE2 receptor and viral target main protease. In combination of the docking results, the natural abundance of the substances, and botanical knowledge, we proposed that artemisinin, rutin, glycyrrhizin, cholic acid, hyodeoxycholic acid, puerarin, oleanic acid, andrographolide, matrine, codeine, morphine, chlorogenic acid, and baicalin (or Yinhuang Injection containing chlorogenic acid and baicalin) might be of value for clinical trials during a 2019-nCov outbreak.

COVID-19, caused by the SARS-CoV-2 virus, has spread around the world and killed around 6.9 million people. Rapid and accurate diagnosis is essential for preventing and controlling the disease, reducing transmission and consequently saving lives. RT-PCR is the gold standard test used to detect the disease. However, the test is expensive and the result is time-consuming, which makes mass testing difficult, especially in countries with limited resources. In addition, the test has high analytical specificity and low diagnostic sensitivity, which leads to false-negative results. Several studies in the literature report the presence of hematological and biochemical alterations in infected patients and use these alterations with machine learning algorithms to help diagnose the disease. Therefore, this article presents the results obtained by different neural network architectures based on Adaptive Resonance Theory (ART) for the diagnosis of COVID-19. The study was conducted in two distinct stages: the first consisted of selecting the best ART network among several, using three open-access datasets and comparing the results with the literature. In the second stage, the chosen model was tested on a dataset containing patients from various hospitals in four countries. In addition, the model was subjected to external validation, including data from a country not present during the training and adjustment of the model, in order to validate the robustness and generalization capacity of the model. The results obtained by the ART networks in this study are promising, outperforming not only classical models, but also the deep learning models often used in the literature. Validation on data from different countries strengthens the model’s reliability and effectiveness.

Background: A new coronavirus (SARS-CoV-2) that emerged from Wuhan, Hubei Province, China, has spread throughout the world and is declared a pandemic by the World Health Organization (WHO). A lot remains to be understood of SARS-CoV-2 and the disease (COVID-19). SARS-CoV-2 has until recently been identified as responsible for both asymptomatic and serious life-threatening infections. The unavailability of specific therapeutic agents is a major hurdle in the treatment and management of COVID-19 patients. The present review attempts to evaluate the immunobiochemical aspects of the pathogenesis, diagnosis, and management of SARS-CoV-2 infection. Main Body: This review is a comprehensive evaluation of the data collected through various sources, including Google Scholar, PubMed, and Scopus. The articles were searched and selected using key words such as “Coronavirus disease (COVID-19)”, “Diagnosis of COVID-19”, Pathogenesis of Covid-19”, “management of COVID-19”, “Immunology of COVID-19”, and “Complications of COVID-19”. The study noted that the novel Coronavirus infection could result in an exaggerated immune response, causing a cytokine storm and damaging several organs of the body. The infected patients develop several complications, including immunological, hematological, and biochemical alterations. Consequently, COVID-19 patients may develop cardiovascular, liver, renal, and neurological complications, among others. Conclusion: An increased understanding of the immunobiochemical aspects of the disease may contribute to better management of SARS-CoV-2-infected persons, as evidenced from the available literature. A holistic approach to the management of COVID-19 patients taking into consideration the effect of COVID-19 infection on various organs of the body assumes increased significance in patient management.

Coronavirus is now a significant human pathogen with the emergence of SARS-CoV-2. Until now there has been no data to support a threat to agricultural industries. Using a comparative genomic protein analysis, this study examined the angiotensin-converting enzyme II (ACEII) gene of 17 animal species with an emphasis on agriculture. To determine viral vulnerability the 20 known SARS-CoV-2 receptor-binding domain (RBD)/ACEII receptor interaction sites were compared to determine their potential susceptibility to the SARS-CoV-2 virus. With the known bat host’s (XP_032963186) number of binding sites as a threshold, we note that ALL animal species examined in this study contained significant numbers (≥10) of SARS-CoV-2 binding sites and could be at risk for SARS-CoV-2 infection. The data from this study suggest SARS-CoV-2 imposes a grave threat to the safety and security of the agricultural industry. Urgent studies are needed to determine if infected animals can transmit SARS-CoV-2 before and/or after processing.

Introduction: Coronaviruses are zoonotic viruses that include human epidemic pathogens such as the Middle East Respiratory Syndrome virus (MERS-CoV), and the Severe Acute Respiratory Syndrome virus (SARS-CoV), among others (e.g., COVID-19, the recently emerging coronavirus disease). The role of animals as potential reservoirs for such pathogens remains an unanswered question. No systematic reviews have been published on this topic to date. Methods: We performed a systematic literature review with meta-analysis, using three databases to assess MERS-CoV and SARS-CoV infection in animals and its diagnosis by serological and molecular tests. We performed a random-effects model meta-analysis to calculate the pooled prevalence and 95% confidence interval (95%CI). Results: 6,493articles were retrieved (1960-2019). After screening by abstract/title, 50 articles were selected for full-text assessment. Of them, 42 were finally included for qualitative and quantitative analyses. From a total of 34 studies (n=20,896 animals), the pool prevalence by RT-PCR for MERS-CoV was 7.2% (95%CI 5.6-8.7%), with 97.3% occurring in camels, in which pool prevalence was 10.3% (95%CI 8.3-12.3). Qatar was the country with the highest MERS-CoV RT-PCR pool prevalence, 32.6% (95%CI 4.8-60.4%). From 5 studies and 2,618 animals, for SARS-CoV, the RT-PCR pool prevalence was 2.3% (95%CI 1.3-3.3). Of those, 38.35% were reported on bats, in which the pool prevalence was 14.1% (95%CI0.0-44.6%). Discussion: A considerable proportion of infected animals tested positive, particularly by nucleic acid amplification tests (NAAT). This essential condition highlights the relevance of individual animals as reservoirs of MERS-CoV and SARS-CoV. In this meta-analysis, camels and bats were found to be positive by RT-PCR in over 10% of the cases for both; thus, suggesting their relevance in the maintenance of wild zoonotic transmission.

When working with the novel coronavirus SARS-CoV-2 during a pandemic response, having a rapid, reproducible and reliable assay for infectious virus quantitation and utilization for evaluation of potential therapeutics is critical. Compared to traditional agarose overlay plaques visualized with neutral red, assays performed with Avicel R RC-591 semi-solid overlay provide a simplified format for rapid and easy detection and neutralization testing. The method is easily modified for higher throughput using dispensers or automated processing. Fixation using formalin provides flexibility when dealing with pathogenic agents such as SARS-CoV-2 where tissue culture plates might be removed from biocontainment for staining. Although plaque assays are considered straightforward in principle, having an easily reproducible, consistent plaque assay is an invaluable tool.

The human angiotensin-converting enzyme 2 (ACE2) has a crucial role on blood pressure control; however, ACE2 is also the primary SARS-CoV-2 (S domain) virus receptor. Inhibiting or even reducing the expression of the native ACE2 might diminish the viral entry into the cells, but may cause a failure of ACE2 biological activity, primarily in patients with comorbidities, including diabetes mellitus or hypertension. Since the ACE2 catalytic site and the SARS-Cov-2 receptor are distinct, we designed a Crispr-Cas9 model system, predicting the respective sequences for a guide RNA (gRNA) and a single-stranded oligo dideoxy nucleotide (ssODN), to introduce point mutations into the exon 1 of the human ACE2 gene, which encodes the alpha-helix, implicated on the binding of the SARS-CoV-2 envelope S protein. Protein modeling predicted that the specific substitutions of residues Phe28, Lys31, and Tyr41 for Ala at the ACE2 alpha-helix do not significantly alter ACE2 native conformation. The analysis of the impact of these mutations on ACE2 receptor function predicted a weakening of the binding of the SARS-CoV-2 protein S. An experimental genome editing of cells based on these Crispr-Cas9 elements might reduce the SARS-CoV-2 ability to enter the epithelial cell, preserving the biological activity of ACE2 enzyme.

A novel coronavirus, named 2019-nCoV, is responsible for current epidemic outbreaks in China and also other countries that cause acute pneumonia that was primarily linked to a seafood wholesale market in Wuhan, China. To control and prevent the existing epidemic outbreaks of coronavirus in China, a precise and easy disinfection/sterilization technique is important to disinfect/sterilize the mass-level peoples and their ambient environments (e.g. atmospheric air/aerosols). Among the disinfection techniques, control fire/flame (CF) could be applied. Large-size CF (LSCF) can be generated by using gas burner, gas cylinder that used in restaurant, coals, kerosene (petroleum), dried straws, dried woods) at entry and exit points of big gathering locations (e.g. hospital, airport, rail stations, seaports, apartments, streets/roads, etc. Additionally, small-size CF (SSCF) can be produced by using gas burner of kitchen, electric heater, kindle or waste papers at individual home and ward/room at hospital. Individual person can be soaked/immersed their hands and their belongings nearby CF for a moment, likely followed sterilization during quantification of the number of bacteria in experimental observation, that can rapidly sterilize the person perfectly. Correspondingly, the ambient air/aerosols moved towards CF due to water evaporation by fire that subsequently refresh all ambient air/aerosols by killing all viruses. Such CF could certainly reach the temperature higher than 56 degree C that could effectively disinfect/sterilize/kill the coronavirus. Therefore, CF could be effectively applied to control and prevent the epidemic outbreaks of coronavirus across China and worldwide.

A lot of research studies have been surveyed the completed genomes of prokaryotic and eukaryotic and focused on the correlation between the percentage of microsatellite sequences in completed genomes and the whole size of the organism genomes. There are fewer studies made in repetitive sequences otherwise simple sequence repeats or long tandem repeats of virus genomes. simple sequence repeats (SSRs) are the most important regions for recombination and moving repeats blocks from site to another site in the genomes. A tool was programmed and designed by visual basic 6.0 to find the long tandem repeats in DNA sequences of the small genomes. The tool named “Repeater Finder Regular Expression”, (RFRE) Version 1.0, 2016. The tool was utilized to discover different pattern of long tandem repeats (LTR) motifs on the completed genomes of human corona virus strains by using a joined regular expression language. In this study, a twenty-nine accession numbers of human coronavirus completed genomes, (hku1) strains were retrieved from the Genbank. The researcher can write a different regular expression patterns and joined regular expression patterns through the designed tool to search and find a specific motif of nucleotide sequences inside the complete genomes. The RFRE tool searched and found three different total lengths of a perfect long tandem repeats (240bp, 300bp and 480bp). A Dot plot gave a picture view for the long tandem repeat sequences in the completed genome sequence (KF430201.1) of human coronavirus. The genomic dot plot tool YASS was used as a genomic similarity searching tool to check for the uninterrupted repeats and confirm the sensitivity of the (RFRE) tool. To identify the recombination site in the genomes of human coronavirus the RAT tool was applied to find the recombination sites between the completed genomes of human corona viruses .The RAT tool recognized the recombination site in the nucleotide position (3012) and at the same time this recombination site position (3012) was also recognized as a beginning position of a long tandem repeat. A precise motif was predicted from the translated repeats of Human Corona Virus which found by PRATT tool. There was a relationship between the total length of long tandem repeats and genome size of Human Corona Virus and the correlation value R² was equal to (0,451). In conclusion, this study presented the importance of finding the long tandem repeats of human coronavirus and gives a relationship between the completed genome size of human coronavirus types and long tandem repeats. The nucleotide position (3012) was a hot spot site for a recombination among the complete genomes of human coronavirus and also identified as a repetitive site in the genomes of human corona virus (hku1). The repeats in human coronavirus (hku1) were predicated to be a main major role of virus evolution.

SARS-CoV-2 attachment and entry inside mammalian cells is mainly mediated by human angiotensin-converting enzyme 2 (ACE2) and its interaction with spike protein. However, it is well known that spike protein also interacts with other molecules like glycosaminoglycans (GAG), e.g., heparan sulfate (HS) or Enoxaparin (EX), which are linear, anionically charged polysaccharides known for their biological activities. The mode of action of these two polysaccharides is to bind spike protein to block the interaction with ACE2 receptors. This study aimed to assess a model capable of confirming the activity of these GAGs in both the wild-type strain of SARS-CoV-2 and its variants, such as the highly variable BA.2.86. This was achieved by combining in silico modeling with in vitro determination using BacMam technology. The results showed the antiviral activity of HS and EX both in vitro and through the in-silico analysis, reconciling conflicting findings from recent studies on the cellular entry of SARS-CoV-2. In conclusion, it is possible to highlight the ability of these molecules to circumvent the high variability of SARS-CoV-2, providing valuable insights into intervention strategies targeting cell entry mechanisms and establishing a safe in vitro model.

The Main Protease (Mpro) plays a pivotal role in the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is considered a highly conserved viral target. Disruption of the catalytic activity of Mpro produces a detrimental effect on the course of the infection, making this target one of the most attractive for the treatment of COVID-19. The current success of the SARS-CoV-2 Mpro inhibitor Nirmatrelvir, the first oral drug for the treatment of severe forms of COVID-19, has further focused the attention of researchers on this important viral target, making the search for new Mpro inhibitors a thriving and exciting field for the development of antiviral drugs active against SARS-CoV-2 and related coronaviruses.

Background: Studies have linked bats to outbreaks in human populations such as SARS-CoV-1 and MERS-CoV and the ongoing SARS-CoV-2 pandemic. Method: We carried out a longitudinal survey from August 2020 to July 2021 at two sites in Zimbabwe with bat-human interactions: Magweto cave and Chirundu farm. A total 1732 and 1866 individual bat faecal samples were collected respectively. Coronaviruses and bat species were amplified using PCR systems respectively. Results: Analysis of the coronavirus sequences revealed a high genetic diversity and we identified different sub-viral groups in the Alphacoronavirus and Betacoronavirus genus. The established sub-viral groups fell within the described Alphacoronavirus sub-genera: Decacovirus, Duvinacovirus, Rhinacovirus, Setracovirus and Minunacovirus and for Betacoronavirus sub-genera: Sarbecoviruses, Merbecovirus and Hibecovirus. Our results showed an overall proportion for CoV positive PCR tests of 23.7% at Chirundu site, 16.5% and 38.9% at Magweto site for small insectivorous bats and Macronycteris gigas respectively. Conclusion: The higher risk of bat coronaviruses exposure for humans ranged from December to March in relation to higher viral shedding peaks of coronaviruses in the parturition, lactation and weaning months of the bat populations at both sites. We also highlight the need to further document viral infectious risk in human/domestic animal populations surrounding bat habitats in Zimbabwe.

Nowadays, the human population is facing the third and may be the worst pandemic caused by human coronaviruses (CoVs). The virus was first reported in Wuhan, China on 31 December 2019 and spread within short time to almost all countries of the world. Genome analysis of the early virus isolates has revealed high similarity with SARS-CoV and hence the new virus was officially named SARS-CoV-2. Since CoVs have the largest genome among all RNA viruses, they can adapt many point mutation and recombination events; particularly in spike gene, that enable these viruses to rapidly change and evolve in nature. CoVs are known to cross the species boundaries by using different cellular receptors. SARS-CoV-2 is believed to originate in bats and transmitted to human being through an ill-defined intermediate host. In the current review, different aspects of SARS-CoV-2 biology and pathogenicity are discussed including virus genetics and evolution, spike protein and its role in evolution and adaptation to novel hosts, and virus transmission and persistence in nature. In addition, the immune response developed during SARS-CoV-2 infection is demonstrated with special reference to the interplay between immune cells and their role in disease progression. We believe that SARS-CoV-2 outbreak will not be the last and spillover of CoVs from bats will continue. Therefore, establishing intervention approaches to reduce the likelihood of future CoVs spillover from the natural reservoirs is a priority.

The global use of alcohol based hand sanitizers (ABHS) as a means of controlling the transmission of infectious disease increased dramatically in 2020 as governments and public health agencies across the world advocated hand hygiene as a preventative measure during the COVID-19 pandemic. Although the performance of these products is most commonly defined as a function of their alcohol concentration, they are multifaceted products in which an interplay of several factors is important in determining efficacy. The hand sanitizer tetrahedron, is a novel concept that considers both ABHS formulation factors and product performance factors from a multi-dimensional perspective. The four faces of the tetrahedron represent input/formulation factors: 1) the type and amount of alcohol, 2) inactive ingredients, 3) the type of formulation/delivery system and 4) manufacturing practices. The four corners of the tetrahedron represent output/product performance factors: 1) efficacy, 2) sensory characteristics, 3) usage, usability and compliance and 4) product safety/adverse effects. All factors are of importance to ensuring the effectiveness and utility of these products.

Background: To prioritize the development of antiviral compounds, it is necessary to compare their relative preclinical activity and clinical efficacy. Methods: We reviewed in vitro, animal model, and clinical studies of candidate anti-coronavirus compounds and placed extracted data in an online relational database. Results: As of July 2020, the Coronavirus Antiviral Research Database (CoV-RDB; covdb.stanford.edu) contained >2,400 cell culture, entry assay and biochemical experiments, 240 animal model studies, and 56 clinical studies from >300 published papers. SARS-CoV-2, SARS-CoV, and MERS-CoV account for approximately 85% of the data. Approximately 75% of experiments involved compounds with a known or likely mechanism of action, including receptor binding inhibitors and monoclonal antibodies (20%); viral protease inhibitors (18%); polymerase inhibitors (9%); interferons (8%); fusion inhibitors (8%); host endosomal trafficking inhibitors (7%); and host protease inhibitors (5%). For 724 compounds with a known or likely mechanism, 95 (13%) are licensed in the US for other indications, 72 (10%) are licensed outside the US or are in human trials, and 557 (77%) are pre-clinical investigational compounds. Conclusion: CoV-RDB facilitates comparisons between different candidate antiviral compounds, thereby helping scientists, clinical investigators, public health officials, and funding agencies prioritize the most promising compounds and repurposed drugs for further development.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the disease COVID-19 that has decimated the health and economy of our planet. The virus causes the disease not only in people but also in companion and wild animals. People with diabetes are at risk of the disease. As yet we do not know why the virus is highly successful in causing the pandemic within 3 months of its first report. The structural proteins of SARS include, membrane glycoprotein (M), envelope protein (E), nucleocapsid protein (N) and the spike protein (S). The structure and function of the most abundant structural protein of SARS-CoV-2, the membrane (M) glycoprotein is not fully understood. Using in silico analyses we determined the structure and potential function of the M protein. The M protein of SARS-CoV-2 is 98.6% similar to the M protein of bat SARS-CoV, maintains 98.2% homology with pangolin SARS-CoV, and has 90% homology with M protein of SARS-CoV; whereas, the similarity was only 38% with the M protein of MERS-CoV. In silico analyses showed that the M protein of SARS-CoV-2 has a triple helix bundle, form a single 3-transmembrane domain (TM), and are homologous to the prokaryotic sugar transport protein semiSWEET. SemiSWEETs are related to the PQ-loop family that function as cargo receptors in vesicle transport, mediates movement of basic amino acids across lysosomal membranes, and is also involved in phospholipase flippase function. The advantage and role of the M protein having a sugar transport-like structure is not clearly understood. The M protein of SARS-CoV-2 interacts with S, E and N protein. The S protein of the virus is glycosylated. It could be hypothesized that the sugar transporter-like structure of the M protein influences glycosylation of the S protein. Endocytosis is critical for the internalization and maturation of RNA viruses, including SARS-CoV-2. Sucrose is involved in endosome and lysosome maturation and may also induce autophagy, pathways that help in the entry of the virus. Overall, it could be hypothesized that the semiSWEET sugar transporter-like structure of the M protein may be involved in multiple functions that may aid in the rapid proliferation, replication and immune evasion of the SARS-CoV-2 virus. Biological experiments would validate the presence and function of the semiSWEET sugar transporter.

Analysis of SARS-CoV-2 spike protein sequences of over 19 countries from biological databases submitted around the globe was carried out with help of bioinformatics tools and structure prediction databases. Initial data analysis showed entry of virus into different geographic regions started in the month of January 2020. Meanwhile, alignment of spike protein sequences of SARS-CoV-2 isolates from China and other countries revealed a critical mutation of D614G. Surprisingly, mutation D614G was not seen in early samples submitted in the month of January but gradually it started appearing globally from the month of March 2020. However, the mutations of amino acids in the spike protein other than D614G exhibiting similar pI and altered polarity were found to be specific to geographical regions. Besides, prediction of homology model for interaction of spike protein showed predominant role of chain C of trimeric spike protein in adhering receptor binding domain (RBD) of human ACE2 receptor. Furthermore, the prediction of glycosylation points has revealed that there are about 20 N-glycosylation potential sites on spike protein. We believe that the information present here would not only help in thorough understanding of infectivity but also enhance the knowledge of the scientific community in developing prophylactics and/or therapeutics for SARS-CoV19-2 virus.

Novel severe acute respiratory syndrome coronavirus 2 infection (SARS-Cov-2) is an acute respiratory and infectious disease. This perspective aims to provide the basic understanding of the inflammation caused by SARS-Cov-2 and relation to trigeminal ganglion (TG). Virus enters through the mucous membranes of orofacial region and reach the TG where it resides and take control of its peptides including Substance P (SP).SP is the main neuropeptide, neuromodulator and neuro-hormone of TG, associated with nociception and inflammation under noxious stimulus. SP release is triggered and consequently, it affects the immune cells, blood vessels to release the mediators for inflammation. Cytokine storming is initiated and cause respiratory distress, bronchoconstriction and death in complicated cases. Neurokinin-1 Receptor (NK-1R) antagonist and glucocorticoids may be used to alleviate the symptoms and treat this infection. SP is the main culprit seem to be involved in the triggering of inflammatory pathways in SARS-Cov-2 infection. It has direct association with cardiorespiratory rhythm, sleep-wake cycle, nociception, ventilator responses and regulates many important physiological and pathological roles. Its over-secretion should be blocked by NK-1R antagonist. However, experimental work leading to clinical trials are mandatory for further confirmation.

Since the severe acute respiratory syndrome (SARS) outbreak in 2003, human coronaviruses (hCoVs) have been identified as causative agents of severe acute respiratory tract infections. Two more hCoV outbreaks have since occurred, the most recent being SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19). The clinical presentation of SARS and MERS is remarkably similar to COVID-19, with hyperinflammation causing a severe form of the disease in some patients. Previous studies show that the expression of the SARS-CoV E protein is associated with the hyperinflammatory response that could culminate in acute respiratory distress syndrome (ARDS), a potentially fatal complication. This immune-mediated damage is largely caused by a cytokine storm, which is induced by significantly elevated levels of inflammatory cytokines interleukin (IL)-1beta and IL-6, which are partly mediated by the expression of the SARS-CoV E protein. The interaction between the SARS-CoV E protein and the host protein, syntenin, as well as the viroporin function of SARS-CoV E, are linked to this cytokine dysregulation. This review aims to compare the clinical presentation of virulent hCoVs with a specific focus on the cause of the immunopathology. The review also proposes that inhibition of IL-1beta and IL-6 in severe cases can improve patient outcome.

The severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) viral genome is an RNA virus consisting of approximately 30,000 bases. As part of testing efforts, whole genome sequencing of human isolates has resulted in over 1,600 complete genomes publicly available from GenBank. We have performed a comparative phylogenetic analysis of the sequences, in order to detect common mutations within the population. Analysis of variants occurring within the assembled genomes yields 417 variants occurring in at least 1% of the completed genomes, including 229 within the 5’ untranslated region (UTR), 152 within the 3’UTR, 2 within intergenic regions and 34 within coding sequences.

Objective: To use mathematical models to predict the epidemiological impact of lifting the lockdown in London, UK, and alternative strategies to help inform policy in the UK. Methods: A mathematical model for the transmission of SARS-CoV2 in London. The model was parametrised using data on notified cases, deaths, contacts, and mobility to analyse the epidemic in the UK capital. We investigated the impact of multiple non pharmaceutical interventions (NPIs) and combinations of these measures on future incidence of COVID-19. Results: Immediate action at the early stages of an epidemic in the affected districts would have tackled spread. While an extended lockdown is highly effective, other measures such as shielding older populations, universal testing and facemasks can all potentially contribute to a reduction of infections and deaths. However, based on current evidence it seems unlikely they will be as effective as continued lockdown. In order to achieve elimination and lift lockdown within 5 months, the best strategy seems to be a combination of weekly universal testing, contact tracing and use of facemasks, with concurrent lockdown. This approach could potentially reduce deaths by 48% compared with continued lockdown alone. Conclusions: A combination of NPIs such as universal testing, contact tracing and mask use while under lockdown would be associated with least deaths and infections. This approach would require high uptake and sustained local effort but it is potentially feasible as may lead to elimination in a relatively short time scale.

After the emergence of Severe Acute Respiratory Syndrome Coronavirus(SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in the last two decades, the world is facing its new challenge in SARS-CoV-2 pandemic with unfathomable global responses. The characteristic clinical symptoms for Coronavirus (COVID-19) affected patients are high fever, dry-cough, dyspnoea, lethal pneumonia whereas some patients also show few additional neurological signs such as headache, nausea, vomiting. The accumulative evidences suggest that Coronavirus is not only confined within the respiratory tract and that may also invade in central nervous system (CNS), peripheral nervous system (PNS) inducing some fatal Neurological diseases. Here we analyse the phylogenetic perspective of SARS-CoV2 with other strains of β-Coronaviridae from a standpoint of neurological spectrum disorders. Based on the existing case reports, literature and open data-bases, we also analyse the differential distribution of neurological impairments in COVID-19 positive patients along with angiotensin-converting enzyme-2(ACE2) expression dynamics in neuronal and non-neuronal tissue of central and peripheral nervous system. Besides, we discuss the need for modulations in clinical approach from a neurological point of view, as a measure towards reducing disease transmission, morbidity and mortality in SARS-CoV2 positive patients.

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.

Although phylogenetic analysis shows coronaviruses (CoV) share similar genome sequences, CoVs encode different number of proteins (5 to 14), which has implication on viral pathogenicity and infection. Here, we aimed to identify (in-silico) the similarities between different members of coronavirus family. The analysis included 50 coronavirus proteomes, including SARS-CoV-2 (COVID-19), to find the variation of the number of protein functional motifs and domain in each coronavirus. For this role, we used the experimentally validated domain (motif) that known to be crucial for viral infection. Although human CoVs are classified within one genus, we found variations among them. SARS-CoV-1, SARS-CoV-2 and MERS-CoV encode different type of domains, which has implications on the molecular interactions triggered by each virus within human cells. Secondly, we used functional motifs to reconstruct the potential molecular pathways or interactions triggered by SARS-CoV-2 proteins within human cell.

Recent emergence of novel coronavirus (SARS-CoV-2) all over the world has resulted more than 33,106 global deaths. To date well-established therapeutics modules for infected patients are unknown. In this present initiative, molecular interactions between FDA-approved antiviral drugs against the Hepatitis-C virus (HCV) have been investigated theoretically against the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2. HCV and SARS-CoV-2 are both +ssRNA viruses. At 25^o C beclabuvir, a non-nucleoside inhibitor of the RdRp_HCV can efficiently bind to RdRp _SARS-CoV-2 (ΔG_AutoDock = -9.95 kcal mol^-1) with an inhibition constant of 51.03 nM. Both the ΔG_London and ΔG_{GBVI / WSA} values were - 9.06 and - 6.67 kcal mol^-1, respectively for binding of beclabuvir to RdRp_SARS-CoV-2. In addition, beclabuvir has also shown better binding free energy with RdRp_SARS-CoV-2 (ΔG_vina = -8.0 kcal mol^-1) than that observed with the Thumb 1 domain of RdRp_HCV (ΔG_vina = -7.1 kcal mol^-1). InterProScan has suggested the RNA-directed 5'-3' polymerase activity exists within 549^th to 776^th amino acid residues of RdRp_SARS-CoV, where the major amino acid residues interacting being I591, Y621, C624, D625, A690, N693, L760, D762, D763, and E813-N817. Molecular interaction suggests occupancy of beclabuvir inside the active site environment of the RdRp_SARS-CoV-2, the enzyme essential for viral RNA synthesis. In conclusion, results suggest beclabuvir may serve as an anti-SARS-CoV-2 drug.

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 (coronavirus disease 2019) is a public health emergency of international concern caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). As of this time, there is no known effective pharmaceutical, phytopharmaceutical or traditional medicine for cure or prevention of COVID-19, although it is urgently needed. In this review, based on the current understanding of the disease molecular mechanisms of novel Coronavirus SARS-CoV-2 and its closest relative SARS-CoV and other human Coronaviruses, I have identified some naturally occurring plant based substances and Ayurvedic medicinal herbs that could feasibly be tested as a matter of urgency for prevention as well as therapeutic option for COVID-19 in India and other parts of the world. I conclude that dried rhizome of Curcuma longa L. i.e. turmeric, and its active ingredient curcumin may be effective in preventing as well as cure the COVID-19 pandemic due to its proven antiviral activities, this however need to be tested by appropriate clinical trials as research priority.

Base on the sequence of S genes, which encode spike proteins, we previously identified three different types (North American, S INDEL and S large-DEL types) of porcine epidemic diarrhea virus (PEDV) that have re-emerged in Japan since 2013. Base on experimental infections with the North American and S large-DEL types, we also hypothesized that PEDV virulence may be linked to the S1 subunit of the S protein. To test this hypothesis, we have now assayed in gnotobiotic piglets various recombinant PEDVs generated by reverse genetics. Piglets inoculated with CV777 maintained in National Institute of Animal Health, along with piglets infected with a recombinant form of the same virus, developed subclinical to mild diarrhea. In contrast, severe watery diarrhea, dehydration, weight loss, astasia, and high mortality were observed in piglets inoculated with recombinant strains in which the S gene was partially or fully replaced with corresponding sequences from the highly virulent Japanese PEDV isolate OKN-1/JPN/2013. Indeed, symptoms resembled those in piglets inoculated with the OKN-1/JPN/2013, and were especially pronounced in younger piglets. Collectively, the data demonstrate that the S1 subunit of the S protein is an important determinant of PEDV virulence, and advance development of new vaccine candidate.

The human coronaviruses (CoV) include HCoV-229E, HCoV-OC43, HCoV-NL63 and HCoV-HKU1, some known for decades. The severe acute respiratory syndrome (SARS) CoV briefly emerged into the human population but was controlled. In 2012 another novel severely human pathogenic CoV – Middle Eastern Respiratory Syndrome (MERS)-CoV was identified in the Kingdom of Saudi Arabia, where 80% of over 2,000 human cases have been recorded across five years. Targeted research remains key to developing control strategies for MERS-CoV, a cause of mild illness in its camel reservoir. A new therapeutic toolbox being developed in response to MERS is also teaching us more about how CoVs cause disease. Travel-related cases continue to challenge the world’s surveillance and response capabilities and more data are needed to understand unexplained primary transmission. Signs of genetic change have been recorded but it remains unclear whether any impact on clinical disease. How camels came to carry the virus remains academic to the control of MERS. To date, human-to-human transmission has been inefficient, but virus surveillance, characterisation and reporting are key to responding to any future change. MERS-CoV is not currently a pandemic threat; it is spread mainly with the aid of human habit and error.

The COVID-19 pandemic has significantly impacted global health and economies, necessitating the development of effective vaccines against the novel virus. Understanding the structure and function of SARS-CoV-2 is crucial for rational vaccine design. The virus consists of several key proteins, including the spike protein, envelope protein, membrane protein, and nucleocapsid protein. The spike protein plays a crucial role in host cell entry by binding to the angiotensin-converting enzyme 2 (ACE2) receptor on human cells. The replication of the virus within host cells is facilitated by various viral proteins, such as the RNA-dependent RNA polymerase (RdRp) and the main protease (Mpro). Rational vaccine design strategies for SARS-CoV-2 primarily focus on targeting the spike protein due to its role in host cell entry. However, developing vaccines against this protein is challenging due to its highly mutable nature and potential conformational changes. Alternative strategies involve using other viral proteins, such as the nucleocapsid protein, which is conserved and essential for viral replication. Considering T-cell responses in vaccine design is also vital as they play a vital role in controlling viral infections. Vaccines that elicit both antibody and T-cell responses are more likely to provide robust and durable immunity against SARS-CoV-2. Advancements in rational vaccine design for SARS-CoV-2 include mRNA-based vaccines, viral vector-based vaccines, and protein subunit vaccines. However, challenges remain in developing a universally effective vaccine, including the emergence of new SARS-CoV-2 variants and mutations that may affect the efficacy of existing vaccines. In conclusion, rational vaccine design for SARS-CoV-2 requires a comprehensive understanding of the virus's structure and function, targeting key viral proteins, and considering T-cell responses.

Phylogenetic trees of coronaviruses are difficult to interpret because they undergo frequent ge-nomic recombination. Here, we propose a new method, named coloured genomic bootstrap (CGB) barcodes, to highlight the polyphyletic origins of human sarbecoviruses and understand their host and geographic ori-gins. The results indicate that SARS-CoV and SARS-CoV-2 contain genomic regions of mixed an-cestry originating from horseshoe bat (Rhinolophus) viruses. First, different regions of SARS-CoV share exclusive ancestry with five Rhinolophus viruses from Southwest China (RfYNLF/31C: 17.9%; RpF46: 3.3%; RspSC2018: 2.0%; Rpe3: 1.3%; RaLYRa11: 1.0%) and 97% of its genome can be related to bat viruses from Yunnan (China), supporting its emergence in Rhinolophus species of this province. Second, different regions of SARS-Cov-2 share exclusive ancestry with eight Rhi-nolophus viruses from Yunnan (RpYN06: 5.8%; RaTG13: 4.8%; RmYN02: 3.8%), Laos (RpBA-NAL103: 3.3%; RmarBANAL236: 1.7%; RmBANAL52: 1.0%; RmBANAL247: 0.7%), and Cam-bodia (RshSTT200: 2.3%), and 98% of its genome can be related to bat viruses from northern Laos and Yunnan, supporting its emergence in Rhinolophus species of this region. Although CGB barcodes are very useful to retrace the origins of human sarbecoviruses, further investigations are needed to better apprehend the diversity of coronaviruses in bats from Cambo-dia, Laos, Myanmar, Thailand and Vietnam.

This paper examines interlinkages and hedging opportunities between nine major cryptocurrencies for the period between 30 September 2015 and 4 June 2020, which notably includes the coronavirus disease 2019 (COVID-19) outbreak lasting from early 2020 through the end of the sample period. The results of dynamic conditional correlation (DCC) analysis using a minimum connectedness approach show a high degree of correlation between cryptocurrencies throughout the sample period. However, the correlations reach their minimum values during the COVID-19 pandemic, which indicates that cryptocurrencies acted as a hedge or safe haven during the stressful period of the COVID-19 pandemic. The weight of cryptocurrencies was significantly reduced and their hedging effectiveness varied greatly during the pandemic, which indicates that investors’ preferences changed during the COVID-19 period.

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) challenges include understanding what triggered SARS-CoV-2 emergence, how this RNA virus is evolving or how the genomic variability may impact the primary structure of proteins that are targets for vaccine. We analyzed 19471 SARS-CoV-2 genomes and 199,984 spike glycoprotein sequences available at the GISAID database from all over the world and 3335 genomes of other Coronoviridae family members available at Genbank, collecting SARS-CoV-2 high-quality genomes and distinct Coronoviridae family genomes. Here, we identify a SARS-CoV-2 emerging cluster containing 13 closely related genomes isolated from bat and pangolin that showed evidence of recombination, which may have contributed to the emergence of SARS-CoV-2. The analyzed SARS-CoV-2 genomes presented 9632 single nucleotide polymorphisms (SNPs) corresponding to a variant density of 0.3 over the genome, and a clear geographic distribution. SNPs are unevenly distributed throughout the genome and hotspots for mutations were found for the spike gene and ORF 1ab. We describe a set of predicted spike protein epitopes whose variability is negligible. All predicted epitopes for the structural E, M and N proteins are highly conserved. This result favors the continuous efficacy of the available vaccines.

Background: Micronutrients has roles in strengthening and maintaining immune function, but its supplementation and/or deficiency effects on respiratory tract infections are inconclusive. This review aims to systematically assess the associations between micronutrient supplementation or deficiency, with novel coronavirus incidence and disease severity. Methods: Systematic literature searches conducted in 5 electronic databases identified 751 unique studies, of which 33 studies (5 supplementation studies, 1 supplementation and deficiency study, and 27 deficiency studies) were eventually included in this review. Proportions of incidence and severity outcomes in each group, and adjusted summary statistics with their relevant 95% confidence intervaIs (CI) were extracted. Data from 19 studies were pooled in meta-analysis using the generic inverse variance method. Findings: A total of 360,346 patients across 16 countries, with a mean age between 32 and 87.7 years, were involved across 33 studies. All studies were on COVID-19 infections. In individuals without micronutrient deficiency, there was a significant reduction on odds of COVID-19 incidence (pooled OR: 0.37, 95% CI: 0.18, 0.78), and ICU admissions or severe/critical disease onset (pooled OR: 0.26, 95% CI: 0.08, 0.89). Insignificant protective effects were observed on other outcome measures – mortality, ICU admission, progression to respiratory-related complications, severe/critical disease onset or requiring respiratory support and hospitalization rate. Conclusion: The absence of micronutrient deficiency significantly reduced COVID-19 incidence and clinical deterioration in hospitalized patients. Usage of micronutrients as prophylaxis and complementary supplement in therapeutic management of COVID-19 patients may be a promising and cost-effective approach warranting in-depth investigation.

The eruption of COVID-19 patients in 215 countries worldwide has urged for robust predictive methods that can detect as early as possible the size and duration of the contagious disease and also providing precision predictions. In much recent literature reported on COVID-19, one or more essential parts of such investigation were missed. One of the crucial elements for any predictive method is that such methods should fit simultaneously as much data as possible; these data could be total infected cases, daily hospitalized cases, cumulative recovered cases, and deceased cases, and so on. Other crucial elements include sensitivity and precision of such predictive methods on the amount of data as the contagious disease evolved day by day. To show the importance of these aspects, we have evaluated the standard SIRD model and a newly introduced Gaussian-SIRD model on the development of COVID-19 in Kuwait. It is observed that the SIRD model quickly picks up the main trends of COVID-19 development, but the Gaussian-SIRD model provides precise prediction a longer period of time.

The coronavirus disease 2019 (COVID-19) pandemic is the defining global health and socioeconomic crisis of our time and represents the greatest challenge faced by the world since the end of the Second World War. The academic literature indicates that climatic features, specifically the temperature and absolute humidity, are very important factors affecting infectious pulmonary disease epidemics (e.g., SARS, MERS); however, the influence of climatic parameters on COVID-19 remains extremely controversial. The goal of this study is to quantify the existing relationship between several daily climate parameters (temperature, relative humidity, accumulated precipitation, solar radiation, wind direction and intensity, and evaporation), local morphological parameters, and new daily positive swabs for COVID-19, which represents the only parameter that can be statistically used to quantify the pandemic. The daily deaths parameter was not considered because it is not reliable due to frequent administrative errors. Daily data on meteorological conditions and new cases of COVID-19 were collected for the Lombardy area from March 1, 2020, to April 20, 2020. This region in Italy exhibited the largest number of official deaths in the world per million inhabitants, with a value of approximately 1700 per million on june 30, 2020. Moreover, the apparent lethality was approximately 17% in this area, mainly due to the considerable housing density and the extensive presence of industrial and craft areas. The Mann-Kendall test and multivariate statistical analysis showed that none of the considered climatic variables exhibited statistically significant relationships with the epidemiological evolution of COVID-19, at least in the spring months in temperate subcontinental climate areas, with the exception of solar radiation, which was directly related and showed an otherwise low explained variability of approximately 20%. Furthermore, the average temperatures of two highly representative meteorological stations of Molise and Lucania, the most weakly affected by the pandemic. The temperatures at these stations were approximately 1.5°C lower than that in the cities in Lombardy of Bergamo and Brescia, again confirming that a significant relationship between the increase in temperature and decrease in virology from COVID-19 was not evident, at least in the Italian peninsula.

Conservation history of D614 residue is valuable in predicting the consequences of D614G mutation in the SARS-CoV-2 spike glycoprotein (SGP). We report here that the D614 belonged to an extraordinarily conserved, densely hydrophobic eleven amino acid peptide-motif vavlyqdvnct (11-aa), in the Sarbecovirus group and the variant carrying vavlyqdvnct had appeared in Chinese samples and became predominant in several geographical hotspots in late March, 2020. Interestingly a 2009 annotation of SARS-CoV contained the same mutation.

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.

Coronaviruses (CoVs) are positive-stranded RNA viruses that infect humans and animals. Infection by CoVs such as HCoV-229E, -NL63, -OC43 and -HKUI1 leads to the common cold, short lasting rhinitis, cough, sore throat and fever. However, CoVs such as Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and the newest SARS-CoV-2 (the causative agent of COVID-19) lead to severe and deadly diseases with mortality rates ranging between ~1 to 35% depending on factors such as age and pre-existing conditions. Despite continuous global health threats to human, there are no approved vaccines or drugs targeting human CoVs, and the recent outbreak of COVID-19 emphasizes an urgent need for therapeutic interventions. Using computational and bioinformatics tools, here we present the feasibility of reported broad-spectrum RNA polymerase inhibitors as anti- SARS-CoV-2 drugs targeting its main RNA polymerase, suggesting that investigational and approved nucleoside RNA polymerase inhibitors have potential as anti-SARS-CoV-2 drugs. However, we note that it is also possible for SARS-CoV-2 to evolve and acquire drug resistance mutations against these nucleoside inhibitors.

Coronavirus Disease 2019 (Covid-19) was first described in December 2019 in Wuhan, Hubei Province, China; and produced by a novel coronavirus designed as the acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Covid-19 has become a pandemic reaching over 1.3 million confirmed cases and 73,000 deaths. Several efforts have been done to identify pharmacological agents that can be used to treat patients and protect healthcare professionals. The sequencing of the virus genome not only has offered the possibility to develop a vaccine, but also to identified and characterize the virus proteins. Among these proteins, main protease (M^pro) has been identified as a potential therapeutic target, since it is essential for the processing other viral proteins. Crystal structures of SARS-CoV-2 M^pro and inhibitors has been described during the last months. To describe additional compounds that can inhibit SARS-CoV-2 M^pro, in this study we performed a molecular docking-based virtual screening against a library of experimental and approved drugs. Top 10 hits included Pictilisib, Nimorazole, Ergoloid mesylates, Lumacaftor, Cefuroxime, Cepharanhine, and Nilotinib. These compounds were predicted to have higher binding affinity for SARS-CoV-2 M^pro than previously reported inhibitors for this protein, suggesting a higher potential to inhibit virus replication. Since the identified drugs have both pre-clinical and clinical information, we consider that these results may contribute to the identification of treatment alternative for Covid-19. Nevertheless, in vitro and in vivo confirmation should be performed before these compounds could be translated to the clinic.

SARS-CoV-2, the newly identified human coronavirus causing severe pneumonia epidemic, was probably originated from Chinese horseshoe bats. However, direct transmission of the virus from bats to humans is unlikely due to lack of direct contact, implying the existence of unknown intermediate hosts. Angiotensin converting enzyme 2 (ACE2) is the receptor of SARS-CoV-2, but only ACE2s of certain species can be utilized by SARS-CoV-2. Here, we evaluated and ranked the receptor-utilizing capability of ACE2s from various species by phylogenetic clustering and sequence alignment with the currently known ACE2s utilized by SARS-CoV-2, predicting potential intermediate hosts of SARS-CoV-2.

There is a current worldwide outbreak of a new type of coronavirus (2019-nCoV), which originated from China and has now spread to 17 other countries. Governments are under increase pressure to stop the outbreak spiraling into a global health emergency. At this stage, preparedness, transparency and sharing of information are crucial to risk assessments and beginning outbreak control activities. This information should include reports from outbreak sites, and from laboratories supporting the investigation. This paper aggregates and consolidates the virology, epidemiology, clinical management strategies from both English and Chinese literature, official news channels and other official government documents. In addition, by fitting the number of infections with a single-term exponential model, we report that the infection is spreading at an exponential rate, with a doubling period of 1.8 days.

The increase in pandemics caused by RNA viruses of zoonotic origin highlights the urgent need for broad-spectrum antivirals against novel and re-emerging RNA viruses. Broad-spectrum antivirals could be deployed as first-line interventions during an outbreak while virus-specific drugs and vaccines are developed and rolled out. Viruses depend on the host’s protein synthesis machinery for replication. Several natural compounds that target the cellular DEAD-box RNA helicase eIF4A, a key component of the eukaryotic translation initiation complex eIF4F, have emerged as potential broad-spectrum antivirals. Rocaglates, a group of flavaglines of plant origin that clamp mRNAs with highly structured 5’UTRs onto the surface of eIF4A through specific stacking interactions, exhibit the largest selectivity and potential therapeutic indices among all known eIF4A inhibitors. Their unique mechanism of action limits the inhibitory effect of rocaglates to the translation of eIF4A-dependent viral mRNAs and a minor fraction of host mRNAs exhibiting stable RNA secondary structures and/or polypurine sequence stretches in their 5´UTRs, resulting in minimal potential toxic side effects. Maintaining a favorable safety profile while inducing efficient inhibition of a broad-spectrum of RNA viruses makes rocaglates into primary candidates for further development as pan-antiviral therapeutics.

Viral entry is the first stage in the virus replication cycle and, for enveloped viruses, is mediated by virally encoded glycoproteins. Viral glycoproteins have different receptor affinities and triggering mechanisms. We employed vesicular stomatitis virus (VSV), a BSL-2 enveloped virus that can incorporate non-native glycoproteins, to examine the entry efficiencies of diverse viral glycoproteins. To compare glycoprotein-mediated entry efficiencies of: VSV G, SARS-CoV-2 S, EBOV GP, LASV GP, and CHIKV E we produced recombinant VSV (rVSV) viruses that produce the five glycoproteins. The rVSV virions encoded a nano luciferase-PEST (NLucP) reporter gene, which we used in combination with the live-cell substrate Endurazine™ to monitor viral entry kinetics in real time. Our data indicate that rVSV particles with glycoproteins that require more post-internalization priming typically demonstrate delayed entry in comparison to VSV G. In addition to determining the time required for each virus to complete entry, we also used our system to evaluate viral cell surface receptor preferences, monitor fusion, and elucidate endocytosis mechanisms. This system can be rapidly employed to examine diverse viral glycoproteins and their entry requirements.

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly to most parts of the world, causing high numbers of deaths and significant social and economic impacts. SARS-CoV-2 is a novel coronavirus with a suggested zoonotic origin and with the potential for cross-species transmission among animals. Antarctica can be considered the only continent free of SARS-CoV-2 although at the end of the 2019-2020 tourist season, at least one SARS-CoV-2 positive tourist visited the Antarctic Peninsula. Therefore, concerns have been expressed regarding the potential human introduction of this virus to the continent through the activities of research or tourism with potential effects including those related to human health, but also the potential for virus transmission to Antarctic wildlife. This reverse-zoonotic transmission risk to Antarctic wildlife is assessed considering the available information on host susceptibility, dynamics of the infection in humans, and contact interactions between humans and Antarctic wildlife. Measures to reduce the risk are proposed as well as the identification of knowledge gaps related to this issue.

In this article, we analyse the computer aid screening method of COVID19 using Xray and CT scan images. The main objective is to set an analytical closure about the computer aid screening of COVID19 among the X-ray image and CT scan image. The computer aid screening method includes deep feature extraction, transfer learning and traditional machine learning image classification approach. The deep feature extraction and transfer learning method considered 13 pre-trained CNN model. The machine learning approach includes three sets of features and three classifiers. The pre-trained CNN models are alexnet, googlenet, vgg16, vgg19, densenet201, resnet18, resnet50, resnet101, inceptionv3, inceptionresnetv2, xception, mobilenetv2 and shufflenet. The features and classifiers in machine learning approaches are GLCM, LBP, HOG and KNN, SVM, Naive bay’s respectively. In addition, we also analyse the different paradigms of classifiers. In total, the comparative analysis is carried out in 65 classification models, i.e. 13 in deep feature extraction, 13 in transfer learning and 39 in machine learning approaches. Finally, all the classification models perform better in X-ray image set compare to CT scan image set.

The COVID-19 pandemic has revealed many knowledge gaps with implications toward the speed and nature of our response to contain, assess and mitigate risk. The routine discharge of treated and untreated wastewater into rivers and coastal waters has placed SARS-CoV-2 viability in wastewater at the centre of an emerging hazard and potential risk to water industry workers and the public who come into contact with sewage-impacted water. Here we provide a review of the Severe Acute Respiratory Syndrome coronavirus primary literature that presents the evidence base pertaining to the key questions of whether the SARS-CoV-1 and SARS-CoV-2 is shed in stool and urine, is recoverable, and infectious in wastewater. We discuss the challenges posed by the current literature base and the extent to which the current evidence is fit for the purpose of informing robust human and environmental risk assessments.

A micro decision-making utility model under uncertainty is presented as a complementary foundation for macro coronavirus models. The micro model consists of two functions, a risk averse utility function depending on wellness and a wellness random output which is a function of the input variable called “treatment” consisting of such elements as social distance, washing hands, wearing a face mask, and others. The decision maker selects a level of treatment that maximizes her/his expected utility, given the probabilities of the respective outputs. The focus is on how changes in a person’s psychological attitude towards the macro determined (announced) probabilities affects the optimum results of the model. Such changes create a micro-macro dynamic interaction which is briefly outlined. A short discussion of the model’s behavioral implications for health policy is also given.

Covid-19 pandemic has captivated scientists to investigate if this new disease can affect the central nervous system (CNS). The most challenging symptoms of Covid-19 are related to respiratory distress, and most patients admitted in intensive care units cannot breathe by their own. Therefore, a crucial question is if respiratory distress can be partially explained by the CNS affection. SARS-Cov-2 is a beta-coronavirus that shares high similarities with SARS-CoV. The infection of SARS‐CoV has been reported in the brains from both patients and experimental animals, where the brainstem was heavily infected. Those coronaviruses have been able to invade the brainstem via a synapse‐connected route to the medullary respiratory center, where the infected regions included the nucleus of the solitary tract and nucleus ambiguous. The vagal afferent nerves from receptors in the lung communicate with the medulla and pons respiratory control centers to coordinate inspiration and expiration. This suggests that neuroinvasion of SARS‐CoV‐2 might play a role in the acute respiratory failure of Covid-19. Therefore, acute respiratory distress in Covid-19 can be partially explained by brainstem dysfunction, suggesting the needs of more specific and aggressive treatments with the direct participation of neurologists and neurointensivists.

Almost half of the confirmed COVID-19 cases detected so far in the United Kingdom are part of a large cluster of 13 British nationals who tested positive for SARS-CoV-2 in the UK, Spain, and France. Transmissions among this cluster occurred at a ski resort in France, and originated from a single infected traveller returning from a conference in Singapore where he acquired the virus. At least 21 individuals were exposed to the virus, tested, and quarantined, with 13 of those testing positive between the period of 6th Feb and 15th Feb. Here, all publicly available information about the primarily UK/France cluster is consolidated, providing a complete and accessible summary of the cases and their connections. Notable in this cluster are the number of individuals infected, the apparent absence of any severe illness among those infected, and a case of a `delayed positive' test during isolation after initially testing negative, at least 7 days after last possible contact.

Monoclonal antibodies (mAbs) are an important treatment option for COVID-19 caused by SARS-CoV-2, especially in immunosuppressed patients. However, this treatment option can become ineffective due to mutations in the SARS-CoV-2 genome, mainly in the receptor binding domain (RBD) of the spike (S) protein. In the present study 7950 SARS-CoV-2 positive samples from the Uppsala and Örebro regions of central Sweden collected between March 2022 and May 2023 were whole-genome sequenced using next-generation sequencing, mainly with the Nanopore sequencing method. Pango lineages were determined and all single nucleotide polymorphism (SNP) mutations that occurred in these samples were identified. The dominant sublineages changed over time and mutations conferring resistance to currently available mAbs became common. Notable ones are R346T and K444T mutations in the RBD that confer significant resistance against tixagevimab and cilgavimab mAbs. Further, mutations conferring a high-fold resistance to bebtelovimab, such as the K444T and V445P mutations, were also observed in the samples. This study highlights that resistance mutations have over time rendered currently available mAbs ineffective against SARS-CoV-2 in most patients. Therefore, there is a need for continued surveillance of resistance mutations and the development of new mAbs that target more conserved regions of the RBD.

In post mortem analyses, SARS-CoV-2 was found in the middle ear of some, but not all patients with COVID-19 disease. It is not clear whether SARS-CoV-2 penetrated the ear passively post mortem, or existed in the middle ear of living patients during, and perhaps also after infection. This study investigates whether SARS-CoV-2 can be found in the middle ear of living patients during ear surgery. Swabs from the nasopharynx, the filter connected to the tracheal tube and secretion from the middle ear were collected during middle ear surgery. All samples were tested for the presence of SARS-CoV-2 with PCR. History of vaccination, COVID-19 and contact with SARS-CoV-2-positive individuals were recorded preoperatively. Postoperative SARS-CoV-2 infection was noted at the follow-up visit. Overall 63 participants (62%) were children and 39 (38%) were adults. SARS-CoV-2 was found in the middle ear and in the nasopharynx of two and four CovEar Study participants, respectively. The filter connected to the tracheal tube was sterile in all cases. Cycle threshold (ct) values of the PCR test were between 25.94 and 37.06. SARS-CoV-2 penetrates into the middle ear of living patients and can be found in asymptomatic patients. The presence of SARS-CoV-2 in the middle ear may have implications for ear surgery and can pose a risk of infection for operating room staff. It may also directly affect the audio-vestibular system.

Coronavirus (COVID-19) gained and will continue to gain a lot of global attention over the coming months (and maybe the coming few years). Since its outbreak in Wuhan (China), it has turned into one of the major challenges affecting the whole world. In a comparatively short time, the virus outbreak turned into a pandemic that led to massive negative impacts not only on people health and well-being, but also on the global economy, travel industry, pharmaceutical industry, tourism industry, and many other industries. This research paper aims to investigate the different effects of coronavirus on the global Halal tourism and Halal hospitality industry and whether the coronavirus pandemic is the end of Halal tourism and hospitality as we know it or not. The paper offers an in-depth theoretical examination of the different aspect of the pandemic on Halal tourism and hospitality industry and provides guidance on how to address these different aspects. The current paper is one of very few research papers addressing coronavirus on the tourism and hospitality industry.

The research problem was formulated as a question: are demand-supply shocks affecting the opening up of a negative or positive output gap? The hypothesis was formulated: demand-supply shocks have a significant impact on the opening up and deepening of the negative output gap, thereby causing real GDP to shrink or potential GDP to grow. The spatial range applies to Poland and the time period - 2008:Q1-2019:Q4. The methodology consists of three stages: the first is the decomposition of the time series using the TRAMO/SEATS on the components: seasonality, trend-cycle, irregular; the second - the decomposition of the trend-cycle component using the Hodrick-Prescott filter into two separate components; the third is the calculation of the output gap; forecast with VECM and IRF approximation. The ouput gap is in the range of - 11% to +10%. After cleaning it, the shock elements are between -2.2% and 2%. Demand-supply shocks open up and widen the negative output gap. Based on forecasts, the output gap will be positive by the end of 2022, close to 0% (optimal scenario), rising to 5% (optimistic scenario) and negative, deepening to -4% (pessimistic scenario). Two of these scenarios point to a growing risk of secular stagnation.

There is a long trail of research studies testing the in vitro and in vivo efficacy of chloroquine and its derivatives in treating and preventing infection by various coronavirus species. More recent findings have highlighted the possibility of treating patients infected with the 2019 novel coronavirus, SARS-CoV-2. This review describes the mechanism of coronavirus infection, the mechanism of action of chloroquine, and summarizes the available literature highlighting the efficacy of chloroquine as an anti-coronavirus agent. These findings should encourage the wider scientific community to conduct thorough research on the possible efficacy of chloroquine and its derivatives in treating and preventing SARS-CoV-2 infection.

This study describes the development of an automated bag valve mask (BVM) compression system, which, during acute shortages and supply chain disruptions can serve as a temporary emergency ventilator. The resuscitation system is based on the Arduino controller with a real-time operating system installed on a largely RepRap 3-D printable parametric component-based structure. The cost of the system is under $170, which makes it affordable for replication by makers around the world. The device provides a controlled breathing mode with tidal volumes from 100 to 800 milliliters, breathing rates from 5 to 40 breaths/minute, and inspiratory-to-expiratory ratio from 1:1 to 1:4. The system is designed for reliability and scalability of measurement circuits through the use of the serial peripheral interface and has the ability to connect additional hardware due to the object-oriented algorithmic approach. Experimental results demonstrate repeatability and accuracy exceeding human capabilities in BVM-based manual ventilation. Future work is necessary to further develop and test the system to make it acceptable for deployment outside of emergencies in clinical environments, however, the nature of the design is such that desired features are relatively easy to add with the test using protocols and parametric design files provided.

The genetic diversity of coronavirus (CoV) is high, and its infection in animals has not yet been fully revealed. By RT-PCR detection of partial RNA dependent RNA polymerase (RdRp) gene of CoV, we screened a total of 502 small mammals belonging to 18 species in 12 genera and 4 orders collected in Dali and Nujiang Prefecture of Western Yunnan Province, China. The prevalence of β-CoV in Chevrieri's field mouse (Apodemus chevrieri) and Lancangjiang field mouse (A. ilex) were 3.54% (4/113) and 6.67% (6/90), respectively; the prevalence of α-CoV in White-footed Indochinese rat (Rattus nitidus) and long-tailed red-toothed shrew (Episoriculus leucops) was 75% (3/4) and 5.88% (1/17), respectively. The co-infection rates of β-CoV and α-CoV in Kachin red-backed vole (Eothenomys cachinus), Norway rat (R. norvegicus) were 2.22% (2/90), 3.85% (1/26) respectively. The identity of the partial RdRp genes obtained of 13 strains of β-CoV was 83.42%-99.23% at nucleotide level, and it is worth noting that the two strains from Kachin red-backed vole showed highly homology to BOV-36/IND/2015 from Indian bovine and DcCoV-HKU23 from one-humped camel (Camelus dromedarius) in Morocco, the nucleotide similarity between 97.86%-98.33%. Similarly, the identity of the 7 strains of α-CoV among the partial RdRp sequences was 94.00%-99.18% at nucleotide levels. The viral load in different tissues was measured by quantitative RT-PCR (qRT-PCR). The average CoV viral load in small mammalian intestinal tissue was 1.25×106copies/g, differently, the mean CoV viral load in liver, heart, lung, spleen and kidney tissue was from 1.29×103 to 4.02×103copies/g, which revealed that CoV has extensive tropism of intestinal tissue in small mammals (P < 0.0001). This result revealed the genetic diversity, epidemiology, and infective tropism of α-CoV and β-CoV in small mammals from Dali and Nujiang, which deepens the comprehending of the retention and infection of coronavirus in natural hosts.

We aimed to explore student and staff perceptions and experiences of a pilot COVID-19 asymptomatic testing service (P-ATS) in a UK university campus setting. This was a mixed-method study comprised of an online survey, and thematic analysis of qualitative data from interviews and focus groups conducted at the end of the 12-week P-ATS programme. Ninety-nine students (84.8% female, 70% first year; 93.9% P-ATS participants) completed an online survey, 41 individuals attended interviews or focus groups, including 31 students (21 first year; 10 final year) and 10 staff. All types of testing and logistics were highly acceptable (virus: swab, saliva; antibody: finger prick) and 94.9% would participate again. Reported adherence to weekly virus testing was high (92.4% completed ≥6 tests; 70.8% submitted all 10 swabs; 89.2% completed ≥1 saliva sample) and 76.9% submitted ≥3 blood samples. Students tested to ‘keep campus safe’, ‘contribute to national efforts to control COVID-19’, and ‘protect others’. 31.3% had high anxiety as measured by the Generalized Anxiety Disorder scale (GAD-7) (27.1% of first year). Students with lower levels of anxiety and greater satisfaction with university communications around P-ATS were more likely to adhere to virus and antibody tests. Increased adherence to testing was associated with higher perceived risk of COVID-19 to self (virus) and others (antibody). Qualitative findings revealed 5 themes and 13 sub-themes: ‘emotional responses to COVID-19’, ‘university life during COVID-19’, ‘influences on testing participation’, ‘testing physical and logistical factors’ and ‘testing effects on mental wellbeing’. Asymptomatic COVID-19 testing (virus/antibodies) is highly acceptable to students and staff in a university campus setting. Clear communications and support for mental wellbeing is likely to be important for testing uptake and adherence. Strategies are needed to facilitate social connections and mitigate the mental health impacts of COVID-19 and self-isolation.

This paper aims to quantify the effect of the deadly novel coronavirus (COVID-19) pandemic outbreak on Chinese stock market performance. Shanghai Stock Exchange Composite Index and its component sector indices are examined in this study. The pandemic is represented by a lockdown dummy, new COVID-19 cases and a dummy for 3 February 2020. First, descriptive analysis is performed on these indices to compare their performances before and during the lockdown period. Next, regression analysis with Exponential Generalized Autoregressive Conditional Heteroscedasticity specification is estimated to quantify the pandemic effect on the Chinese stock market. This paper finds that health care, information technology and telecommunication services sectors were relatively more pandemic-resistant, while other sectors were more severely hurt by the pandemic outbreak. The extent to which each sector was affected by pandemic and sentiments in other financial and commodity markets were reported in details in this paper. The findings of this paper are resourceful for investors to avoid huge loss amid pandemic outburst and the China Securities Regulatory Commission in handling future pandemic occurrence to cool down excessive market sentiments.

Human coronaviruses cause both upper and lower respiratory tract infections in humans. In 2012 a sixth human coronavirus (hCoV) was isolated from a patient presenting with severe respiratory illness. The 60-year-old man died as a result of renal and respiratory failure after admission to a hospital in Jeddah, Saudi Arabia. The aetiological agent was eventually identified as a coronavirus and designated Middle East respiratory syndrome coronavirus (MERS-CoV). MERS-CoV has now been reported in more than 27 countries across the Middle East, Europe, North Africa and Asia. As of July 2017, 2040 MERS-CoV laboratory confirmed cases, resulting in 712 deaths, were reported globally, with a majority of these cases from the Arabian Peninsula. This review summarises the current understanding of MERS-CoV, with special reference to the (i) genome structure, (ii) clinical features, (iii) diagnosis of infection and (iv) treatment and vaccine development.

Papain-like protease PLpro, a domain within a large polyfunctional protein nsp3, plays key roles in the life cycle of SARS-CoV-2, being responsible for the first events of cleavage of a polyprotein into individual proteins (nsp1-4) as well as for the suppression of cellular immunity. Here, we developed a new genetically encoded fluorescent sensor, named PLpro-ERNuc, for detection of PLpro activity in living cells using translocation-based readout. The sensor was designed as follows. A fragment of nsp3 protein was used to direct the sensor on the cytoplasmic surface of endoplasmic reticulum (ER) membrane, thus closely mimicking the natural target of PLpro. The fluorescent part included two bright fluorescent proteins - red mScarlet I and green mNeonGreen, separated by a linker with the PLpro cleavage site. Nuclear localization signal (NLS) was attached to ensure accumulation of mNeonGreen into the nucleus upon cleavage. We tested PLpro-ERNuc in the model of recombinant PLpro expressed in HeLa cells. The sensor demonstrated expected cytoplasmic reticular network in the red and green channels in the absence of protease, and efficient translocation of the green signal into nuclei in the PLpro-expressing cells (14-fold increase of the nucleus/cytoplasm ratio). Then, we used PLpro-ERNuc in the model of Huh7.5 cells infected with SARS-CoV-2 virus, where it showed robust ER-to-nucleus translocation of the green signal in the infected cells 24 h post infection. We believe that PLpro-ERNuc represents a useful tool for screening PLpro inhibitors as well as for monitoring virus spread in a culture.

Background: Feline infectious peritonitis (FIP) is a fatal feline disease classified as either effusive (‘wet’), non-effusive (‘dry’), or a mixture of both forms (‘mixed’). The anti-FIP therapeutic effect of Mutian and molnupiravir, two drugs whose active ingredient is a nucleic acid analog, has been confirmed recently. Methods: Of the cats with FIP, we observed a total of 122 and 56 cases achieved remission after administration of Mutian and molnupiravir as routine treatments, respectively. Changes in clinical indicators suggested to be correlated with FIP remission (weight, hematocrit, and albumin to globulin ratio) before and after the administration of each drug and during follow-up observation were statistically compared for each FIP type. Results: In all three FIP types, administration of either Mutian or molnupiravir resulted in statistically significant increases in these indicators. Furthermore, the effect of Mutian on improving the albumin to globulin ratio was not observed at all in wet FIP, as compared with that of molnupiravir, but statistically significant in mixed and dry (P<0.02 and P<0.003, respectively). These clinical features were all due to differences in fluctuations of circulating globulin levels. Conclusions: These results indicate slight inflammatory responses might be elicited continuously by residual feline coronavirus non-disappeared through molnupiravir treatments.

Although domestic cats are susceptible to infection with SARS-CoV-2, the role of the virus in causing feline disease is less well defined. We conducted a large-scale study to identify SARS-CoV-2 infections in UK pet cats, using active and passive surveillance. Remnant feline respiratory swab samples, submitted for other pathogen testing between May 2021 and February 2023, were screened using RT-qPCR. In addition, we appealed to veterinarians for swab samples from cats suspected of having clinical SARS-CoV-2 infections. Bespoke testing for SARS-CoV-2 neutralising antibodies was also performed, on request, in suspected cases. One RT-qPCR-positive cat was identified from the active surveillance (1/549, 0.18 %), during the Delta wave (1/175, 0.57 %). Passive surveillance detected one cat infected with the Alpha variant, and two of ten cats tested RT-qPCR-positive during the Delta wave. No cats tested RT-qPCR-positive after the emergence of Omicron BA.1 and its descendants although 374 were tested by active and eleven by passive surveillance. We describe four cases of SARS-CoV-2 infection in pet cats, identified by RT-qPCR and/or serology, that presented with a range of clinical signs, as well as their SARS-CoV-2 genome sequences. Our results demonstrate that, although uncommon, clinical infections in cats can and do occur.

Abstract: Our goal is to create point-of-care (POC) strategies that accelerate decision making, increase efficiency, improve outcomes, and enhance standards of care in island communities faced with global warming, rising oceans, population migration, and intensifying weather disasters. We assessed needs in the Bantayan Archipelago and mainland Cebu Province, Visayas Islands, Philippines, to map POC diagnostics, rescue times, and spatial care paths. Significant deficiencies were lack of cardiac troponin testing for rapid diagnosis of acute myocardial infarction, absence of blood gas and pH testing for support of critically ill patients, and geographic gaps prolonging patient transfers and delaying treatment. Strengths comprised primary care that can be facilitated by POC testing, logical inter-island transfers for which decision making and triage could be accelerated with onboard diagnostic testing, and healthcare small-world networks amenable to POC advances, such as pre-hospital testing, that avoid overloading emergency rooms. Healthcare resources must be distributed to archipelago islands, not concentrated in large metropolitan areas inaccessible for emergency interventions. We conclude that a point-of-need focus will help improve public health, decrease disparities in mortality among rural islanders versus urban dwellers, and pave the way for heightened resilience in anticipation of the adverse impact of global warming on vulnerable coastal areas.

Since the detection of the first COVID-19 patient, 2 years have passed, during which more than 287,862,000 people fell ill globally, of which about 1.9% died. Implementation of SARS-CoV-2 control programs required efforts from almost all countries. An important direction in the fight against COVID-19 was the formation of herd immunity, the main tool for managing the pandemic. Study goal: to assess the seroprevalence of antibodies (Abs) to SARS-CoV-2 nucleocapsid (Nc) and receptor binding domain (RBD) in the St. Petersburg population during the COVID-19 pandemic. Materials and methods. A longitudinal cohort randomized monitoring study of Ab seroprevalence (SARS-CoV-2 Nc, RBD) was organized and conducted according to a unified methodology developed by Rospotrebnadzor with the participation of the St. Petersburg Pasteur Institute. For this purpose, a cohort of 1000 volunteers was formed who participated in all five stages of seromonitoring. The cohort was divided into 7 age groups: 1-17; 18-29; 30-39; 40-49; 50-59; 60-69; 70; and older (70+) years. Seropositivity levels (Nc, RBD) were assessed by quantitative and qualitative enzyme immunoassays. During the 2nd year of monitoring, some volunteers were vaccinated with the GamCOVIDVac (84%) or EpiVacCorona (11.6%) vaccines approved in Russia. Statistical processing was carried out using the Excel 2010 software package. Confidence intervals for shares and percentages (95% CI) were calculated using the method of A. Wald and J. Wolfowitz with adjustment (A. Agresti, B.A. Coull). The statistical significance of differences was calculated by z-test, using the appropriate online calculator (p<0.05), unless indicated. Results. There was a trend towards: an increase in Nc seropositivity in stages 1-3 of seromonitoring, with a decrease in stages 4-5 among children and adults. The share of RBD seropositive steadily increased during all 5 stages of seromonitoring. The most frequently found were low anti-RBD Abs levels (22.6-220 BAU/ml). High Ab levels were recorded statistically significantly less frequently. Asymptomatic forms were observed in 84-88% of SARS-CoV-2 seropositive volunteers. By the 5th stage of monitoring, this indicator significantly decreased to 69.8% (95% CI: 66.1-73.4). The monitoring revealed a statistically significant increase in anti-RBD Abs, alongside a statistically significant decrease in the proportion of Nc seropositive. This dynamic was especially characteristic of persons vaccinated with GamCOVIDVac. Conclusion. Prior to the use of specific vaccines, a seroprevalence of anti-Nc Abs was noted. After the introduction of the GamCOVIDVac vaccine in adults, a decrease in the level of anti-Nc Abs was noted due to an increase in the proportion of RBD seropositive persons.

As reported by us and others previously (1, 2), the D614G mutation appeared in the spike glycoprotein (SPG) of the SARS-CoV-2 (the pathogen behind COVID-19) at the early stages of the pandemic and then G614 containing variant of SARS-CoV-2 became the predominant strain in most human populations across the world. However, one of the most recent reports from India (3) stated the incidence of G614 to be only 26% in the Indian population. This report is contradictory to the information available through the GenBank (4) SARS-CoV-2 sequence deposits made by various laboratories from India. The above stated report currently circulating in the Indian media is likely to create a public perception that the Indian strain is less contagious and such a notion could be harmful to people’s welfare. In view of this concern we have re-evaluated, updated and recalculated the incidence of the G614 variant in the Indian population by analyzing 395 Indian SARS-CoV-2 genomic sequences available in the GenBank as of June 26, 2020. In our analysis we have categorized the samples by the month in which the samples were collected. We have used an alignment-free software tool named Compare (5, 6), and the Basic Local Alignment Search Tool (BLAST) (7) in the present analysis. We finally inspected each of the 395 sequences physically for the presence of aspartic acid (D) or glycine (G) at the 614^th position of the spike glycoprotein. We analyzed an Australian cohort in parallel for comparison. We have found that the prevalence of G614 variant in the Indian samples for the month of June 2020 is 90.6%. The trends are similar with the Australian samples.

To mitigate the spread of the COVID-19 coronavirus, some countries have enforced more stringent non-pharmaceutical interventions in contrast to those widely adopted (for e.g. the state of Kuwait). In addition to standard practices such as enforcing curfews, social distancing, and closure of non-essential service industries, other non-conventional policies such as the total confinement of highly populated areas has also been implemented. In this paper, we model the movement of a host population using a mechanistic approach based on random walks, which are either diffusive or super-diffusive. Infections are realised through a contact process, whereby a susceptible host may be infected if in close spatial proximity of the infectious host. Our focus is only on the short-time scale prior to the infectious period, so that no further transmission is assumed. We find that the level of infection depends heavily on the population dynamics, and increases in the case of slow population diffusion, but remains stable for a high or super-diffusive population. Also, we find that the confinement of homogeneous or overcrowded sub-populations has minimal impact in the short term. Finally, we discuss the possible implications of our findings for total confinement in the context of the current situation in Kuwait.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in the current COVID-19 pandemic. Worldwide this disease has infected around 1.5 million individuals with a mortality rate ranging from 5 to 10%. It has also imposed extreme challenges on global health, economy, and social behavior. Due to the unavailability of therapeutics, several efforts are going on in the drug discovery to control the SARS-CoV-2 viral infection. The main protease (M^Pro) plays a critical role in viral replication and maturation, thus can serve as the primary drug target. To understand the structural evolution of M^Pro, we have performed phylogenetic and SSN analysis, that depicted divergence of Coronaviridae M^Pro in five clusters specific to viral hosts. This clustering was also corroborated with the comparison of M^Pro structures. Furthermore, it has been observed that backbone and binding site conformations are conserved despite variation in some of the residues. This conservation can be exploited to repurpose available viral protease inhibitors against SARS-CoV-2 M^Pro. In agreement with this, we performed screening of the custom-made library of ~7100 molecules including active ingredients present in the Ayurvedic anti-tussive medicines, anti-viral phytochemicals and synthetic anti-virals against SARS-CoV-2 M^Pro as the primary target. We identified several natural molecules that strongly binds to SARS-CoV-2 M^Pro among which top seven molecules are d-Viniferin, Myricitrin, Taiwanhomoflavone A, Lactucopicrin 15-oxalate, Nympholide A, Biorobin and Phyllaemblicin B. Most of the predicted lead molecules are from Vitis vinifera, also reported for anti-tussive and/or antiviral activities. These molecules also showed strong binding with other main targets RdRp and hACE-2. We anticipate that our approach for identification of multi-target-directed ligand will provide new avenues for drug discovery against SARS-CoV-2 infection.

A change in biological properties of the SARS-CoV-2 virus can enhance its transmissibility and virulence, complicate the disease course, and reduce the effectiveness of anti-viral therapy and vaccination. We have studied 16 genetic lineages of the Omicron variant. The viral reproduction course was analyzed based on plaque morphology in the agar layer and the maximum titer in Vero E6 cells. BALB/c mice and Syrian hamsters were used as animal models. Viral load and infectious SARS-CoV-2 titer were determined in the nasal tissue and lungs. The severity of infectious process was assessed using histological methods. An increased plug size was observed in CH.1.1 and BQ.1.2.1 strains after six passages. This was due to substitutions D614G, H655Y, and N764K in the coronavirus S protein. The same changes in gene variants Gamma and BA.1 were caused by the substitution R682W, which is not present in lineages CH.1.1 and BQ.1.2.1. A similar substitution, namely R682P, was observed in the BA.5.1 strain. We characterized BA.1 (as a reference), BA.5.2, and XBB.3 strains in vivo as representatives of the main circulating genetic lineages. For the BA.1 strain, ID50 was 1.3 and 14 TCD50 in Syrian hamsters and BALB/c mice, respectively. An insignificant increase in the BA.5.2 virulence compared to that of BA.1 was noted (ID50 was 07. and 10 TCD50, respectively). The XBB.3 pathogenicity in laboratory animals is similar to that of BA.1 (ID50 was 1.8 and 15 TCD50, respectively). Experiments showed a consistent decrease in the virulence of Omicron strains compared to previously circulating SARS-CoV-2 variants. A co-evolutionary change in amino acid sequences, affecting the conformation of the coronavirus S protein and its surface epitopes in representatives of different genetic lineages, was noted. The emergence of potential proteolysis sites and alterations of the furin cleavage site have been observed in numerous Omicron coronavirus variants.

After an incubation period of weeks to months up to 14% of cats infected with feline coronavirus (FCoV) develop feline infectious peritonitis (FIP): a potentially lethal pyogranulomatous perivasculitis. The aim of this study was to find out if stopping FCoV faecal shedding with antivirals prevents FIP. Guardians of cats from which FCoV had been eliminated at least 6 months earlier were contacted to find out the outcome of their cats: 27 households were identified containing 147 cats; 13 cats were treated for FIP and 109 others shed FCoV. A 4-7 day course of oral GS-441524 antiviral stopped faecal virus shedding. Follow-up was from 6 months to 3.5 years: 11 of 147 cats died, but none developed FIP. No FIP-recovered cat relapsed. Cats from 8 households recovered from chronic FCoV enteropathy. A previous field study of 820 FCoV-exposed cats was used as a retrospective control group: 37 of 820 cats developed FIP: the difference was statistically significant (p = 0.0038). Conclusions: early treatment of FCoV-infected cats with oral antivirals prevented FIP. Nevertheless, should FCoV be re-introduced into a household then FIP can result. Further work is required to establish the role of FCoV in cats with inflammatory bowel disease.

We conducted many model simulations to understand the causes of the damages of coronavirus (COVID-19) to lung tissue and constructed a diagram showing apparent viral reproduction, immune response and damage accumulation curves. We found that lung damages include virus-caused damage, tissue damage caused by immune responses and tissue damage caused by accumulated wastes. The virus-caused damage is proportional to the phase lag between the viral reproduction curve and the delayed adaptive immune response curve, while waste-induced damage is attributed to imbalance in removing viral, cellular and metabolic by-products. We found that treatment strategies should slow down viral reproduction and speed up immune response, and improve blood micro-circulation in the lungs. Consistent with the strategies, measures are taken to void direct lung infection, strengthen innate responses, promote immune responses, dilute viral concentration in lung tissue, maintain waste removal balance, protect heart and kidneys, control other infections, avoid allergic reactions and other inflammation, etc. We show that medical, dietary, emotional, lifestyle, environmental, mechanical factors, etc. may be simultaneously used to mitigate lung damages and prove that multiple factor health optimization method is magnitudes more powerful than a single factor treatment. Such a method does not depend on molecular specificity and can be used in parallel to antiviral drugs.

The difficulties faced by the society in its goal of reducing mortality and improving the health status during the period of the COVID-19 pandemic showed that it is necessary to develop new approaches in the therapy of infectious diseases, leading to higher treatment efficiency and few side effects. The subject of the present study is the formation and characterization of the proper-ties of stable liposomes loaded with extracts from Bulgarian medicinal plants and monitoring their antiviral action against the human strain of coronavirus OC43 (HCoV-OC43) in vitro. The hydrodynamic diameter and -potential of the liposomes containing each type of payload were determined with DLS and electrokinetics. The encapsulated amount of extracts was evaluated against quercetin and gallic acid by using colourimetric methods. The BALB 3T3 Neutral Red Uptake (NRU) phototoxicity/cytotoxicity assay was used to estimate the safety of the compounds. For assessment of the antiviral activity against HCoV-OC43 of liposomes (Lip) containing medicinal plant extracts, the cytopathic effect inhibition test was used. Measurements of the virucidal activity and the effect on the virus adsorption stage was carried out using the endpoint dilution method, and ∆lgs were calculated by comparison with untreated controls. The estimated photo irritation factors (PIF) for the Lip containing extracts were < 2 which assigns them to the category of non-phototoxic substances. When the extracts were introduced into the liposomes as their carriers, the antiviral activity of the vesicles against the replication of HCoV-OC43 in vitro in-creased by several times compared to their individual activity described in our previous study. The determination of the effect of structures loaded with extracts on the extracellular virions and the stage of their adsorption to sensitive HCT-8 cells proved that the liposomes do not affect directly the viral surface or cell membrane, but only perform a function of carriers of the active substances and the observed result is due solely to the intracellular action of the extracts.

The COVID-19 pandemic first observed in December 2019 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has influenced every individual on the planet. The virus has influenced our lifestyle, education, economy and the environment. Though the vaccines against COVID-19 have provided protection against the disease; new strains of the virus have lowered the efficiency of the vaccines. There is still no effective therapy for the treatment of the disease. Understanding the protein structure of the virus may lead to the development of effective therapies for the disease. We recently mapped the structural proteins and non-structural proteins of SARS-CoV-2. The accessory proteins (Open reading frames, Orfs) of SARS-CoV-2 modulate the host environment to favor virus replication. This paper reports mapping the accessory proteins (Orfs) of SARS-CoV-2.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the etiological agent of the current pandemic worldwide. The pathological condition induced by this pathogen is known as COVID-19 disease. SARS-CoV-2 associated pandemic has been defined as a “public health emergency of international concern” by the International Health Regulation Emergency Committee of the World Health Organization. To date, considerable efforts are in progress to develop more advanced strategies against SARS-CoV-2. Despite the numerous scientific studies published, our knowledge regarding this pathogen is still incomplete, as this virus has been identified only recently. Therefore, scientific investigation of the SARS-CoV-2 has been possible only for a short period of time and effective management of the serious forms of this disease is still lacking. Considerable efforts are in progress worldwide with the purpose to develop more advanced strategies against this pathogen. In this review, we have analyzed the structural and the biological SARS-CoV-2 characteristics and those of other well-known RNA viruses, with the aim to identify possible similarities and analogies between all these pathogens, may be a very useful approach. These infectious agents have been widely studied since several years ago and, a large series of scientific reports are available in the literature regarding this topic. Therefore, focusing on the Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV) and Influenza viruses (IVs), we have collected their historical data, clinical manifestations, pathogenetic mechanisms and related infections. Taking advantage of the results of our research, we have assembled this narrative review, with the aim to get useful insights and lessons from HIV, HCV and IVs characteristics and, consequently, to transfer the obtained knowledge to the study of SARS-CoV-2 biology. There are well known differences between all these pathogens. In particular, they present a distinct mode of transmission, as SARS-CoV-2 and Influenza viruses are airborne pathogens, whereas HIV and HCV are bloodborne infectious agents. However, these viruses exhibit some potential common clinical manifestations and pathogenetic mechanisms and their understanding may contribute to establishing preventive measures and new therapies against SARS-CoV-2. Accordingly, we have analysed and discussed the following points: 1) the biology, the pathogenesis and the clinical manifestations of SARS-CoV-2, HIV, HCV and IVs in mankind; 2) the onset and spreading of pandemics caused by respiratory viruses according to a perspective historical point of view; 3) the possible development of a persistent SARS-CoV-2 reservoir worldwide; 4) the possibility of SARS-CoV-2 reinfection/reactivation; 5) the possible involvement and impact of climatic factors in increasing the risk of SARS-CoV-2 spreading.

How can neuroscience help everyone to live and care for our confined brains? Understanding and studying human behaviour allows us to measure the impact of such confinement on each of us and to identify those who need help. The challenges are to understand the psychological repercussions following confinement and to understand how neuroscience and neurotechnology can be very interesting tools for dealing with the health crisis. Neuroscience is changing our traditional philosophical and ethical views by providing information about the biological basis of our moral behaviour. The exception of the brain is at the heart of neuroethical thinking and discourse. Neuroethics is an interdisciplinary discipline placed at the intersection between the human sciences and the neurosciences, and aims to help understand how knowledge and research in neurosciences and neurotechnologies will affect the future of society, their impact on humans, relationships, daily life, the labour market ... but also how they can help and provide solutions and answers to the questions of citizens in a health crisis. But it's a double-edged sword, collecting and analyzing brain data in real time seems to be increasingly simple and within everyone's reach, without having the hindsight of the real meaning of these data, allowing one day to read people's thoughts, control them and manipulate them. It is becoming clear that the boundaries between medical and non-medical uses of neuroscience and neurotechnology are becoming very porous, inviting us to reflect on neuroethical issues in order to put safeguards on these uses.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for the disease COVID-19 has wreaked havoc on the health and economy of humanity. In addition, the disease is observed in domestic and wild animals. The disease has impacted directly and indirectly every corner of the planet. Currently, there are no vaccines and effective therapies for COVID-19. SARS-CoV-2 is an enveloped virus with a single-stranded RNA genome of 29.8 kb. More than two-thirds of the genome comprises Orf1ab encoding 16 non-structural proteins (nsps) followed by mRNAs encoding structural proteins, spike (S), envelop (E), membrane (M), and nucleocapsid (N). These genes are interspaced with several accessory genes (open reading frames [Orf] 3a, 3b, 6, 7a, 7b, 8, 9b, 9c and 10). The functions of these proteins are of particular interest for understanding the pathogenesis of SARS-CoV-2. Several of the nsps (nsp3, nsp4, nsp6) and Orf3a are transmembrane proteins involved in regulating the host immunity, modifying host cell organelles for viral replication and escape and hence considered drug targets. In this paper we report mapping the transmembrane structure of the non-structural proteins of SARS-CoV-2.

The coronavirus disease 2019 (COVID-19) was officially declared a pandemic on the 11^th March 2020. It is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), impacting the lower respiratory tract. International travel to Australia during the early stages of the pandemic prior to border closure provided avenues for this virus to spread into Australia. There is little understanding of the clonality of SARS-CoV-2 isolates in Australia, and where they originated. This study aimed to investigate the clonality and ancestral sources of SARS-CoV-2 isolates in Australia using in silico methods. We retrieved 1,346 complete genomes from Australia along with 153 genomes from other countries from the NCBI nucleotide database and Global Initiative On Sharing All Influenza Data (GISAID). We then constructed a representative population of 270 sequences for downstream phylogenetic analysis and ancestral area reconstruction. Overall, two major clusters, one stemming from Europe and another from Asia, especially East Asia, were observed, implying at least two major transmission events with subsequent clades confirming the multiclonality of Australian isolates. We also identified three potential dissemination routes of SARS-CoV-2 into Australia. This study supports the hypothesis of multiple clonality and dispersals of SARS-CoV-2 isolates into Australia.

Propolis, or bee glue, is a complex mixture of resins from plant buds and flowers, wax, pollen and bee saliva. It also contains various vitamins, essential oils, mineral salts, trace elements, hormones and enzymes. It has been found that propolis possesses antimicrobial, antiviral and anti-inflammatory properties. We have studied the antiviral activity of six extracts of Bulgarian propolis collected from six districts of Bulgaria. The study was conducted against structurally different viruses: Human coronavirus strain OC-43 (HCoV OC-43) and Human respiratory syncytial virus type 5 (HRSV-5) (enveloped RNA viruses), Human herpes simplex virus type 1 (HSV-1) (enveloped DNA virus), Human rhinovirus type 14 (HRV-14) (non-enveloped RNA virus) and Human adenovirus type 2 (HadV-2) (non-enveloped DNA virus). The influence of the extracts on the internal replicative cycle of viruses was determined using the cytopathic effect (CPE) inhibition test. The virucidal capacity, their influence on the adsorption stage and their protective effect on uninfected cells were also determined by the end-point dilution method. Residual viral infectivity in propolis samples was compared to untreated controls and Δlgs were calculated. When administered during viral replication, most propolis extracts demonstrated the strongest activity against HCoV OC-43. The influence of propolis extracts on the viability of extracellular virions was expressed to a different degree in the various viruses studied, and the effect was significantly stronger in those with an envelope. Almost all extracts significantly inhibited the step of herpes virus adsorption to the host cell, and some of them showed a protective effect on healthy cells before they were subjected to herpes infection. Our results enlarge the knowledge about the action of propolis and could open new perspectives for its application in viral infections treatment.

Since there is not a clear consensus about the possibility for COVID-19 to be an airborne disease, exists a controversy regarding the need to use surgical masks to prevent its spread. Here, using the Kepler conjecture for ideal packaging, the number of virions of different sizes that can be accommodated inside droplets was calculated and are proportional to the 3^rd potency of the droplet/virion diameter. The differences between particles of 5 um and 100 μm are around four orders of magnitude, explaining why the airborne spread is much more difficult but still possible. There is no solid evidence yet that the airborne coronaviruses may reach enough concentration to infect, but this may be the case under certain circumstances. The WHO partially recognizes now this fact in a warning to health workers (from my point of view too late, as it was the declaration of a pandemic). Another issue is whether the virus stays infective in aerosols generated from patients. This has not been directly proved yet except with artificial aerosols, but there are no reasons why the virus cannot remain in the air and be infective if the viral charge and time of exposure are enough. We must also consider whether the virus can infect the intestine; there are some signs in this sense. Finally, and most importantly, we need to reduce interactions by using surgical masks to flatten the curve, leave the quarantine and avoid a rebound. For cultural reasons, a social distance of 2 meters (2M) is extremely hard to manage. Surgical masks do reduce the interactions in conditions of proximity and, therefore, help to “flatten the curve”. The WHO and CDC “laissez-faire” on this matter do not help and we are running out of time. Anticipated actions, such as the use of surgical masks for the general population, are critical.

The article describes the rational for inhibition of the angiotensin-converting enzyme 2 (ACE2) pathways as specific targets in patients infected by SARS-CoV-2 in order to prevent the establishment of positive feedback loops triggered by COVID-19 in some predisposed subjects. Making use of a large quantity of published reports in which human/rodent ACE2 pathway inhibitors were administered in vivo, it is hypothesized a possible therapeutic pharmacological intervention through an inhibition strategy of the zinc metalloprotease ACE2 and its downstream pathway for SARS-CoV-2 patients. Of even more interest, metal (zinc) chelators and renin inhibitors (both FDA approved drugs) may also work alone or in combination in inhibiting the positive feedback loops, initially triggered by COVID-19 and subsequently sustained by hypoxia independently on viral trigger, when both arms of renin-angiotensin system (ACE2 and ACE) are upregulated, leading to critical, advanced and untreatable stages of the disease.

It is important to be able to detect and differentiate between distinct porcine enteric coronaviruses that can cause similar diseases. However, the existence of naturally occurring recombinant coronaviruses such as swine enteric coronavirus (SeCoV) can give misleading results with currently used diagnostic methods. Therefore, we have developed and validated three duplex real-time quantitative RT-PCR assays for the simultaneous detection of, and differentiation between, porcine epidemic diarrhea virus (PEDV) and SeCoV. Transmissible gastroenteritis virus (TGEV) is also detected by two out of these three assays. In addition, a novel triplex assay was set up that was able to detect and differentiate between these alphacoronaviruses and the porcine deltacoronavirus (PDCoV). The validated assays have low limits of detection, close to 100% efficiency and were able to correctly identify the presence of PEDV and SeCoV in 55 field samples, while 20 samples of other pathogens did not give a positive result. Implementing one or more of these multiplex assays into the routine diagnostic surveillance for PEDV will ensure that the presence of SeCoV, TGEV and PDCoV will not go unnoticed.