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Preprint REVIEW | doi:10.20944/preprints202004.0299.v1

Remdesivir: A Review of Its Discovery and Development Leading to Human Clinical Trials for Treatment of COVID-19

Richard T. Eastman, Jacob S. Roth, Kyle R. Brimacombe, Anton Simeonov, Min Shen, Samarjit Patnaik, Matthew D. Hall

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: SARS-CoV-2; COVID-19; coronavirus; remdesivir

Online: 17 April 2020 (13:02:03 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202012.0710.v1

Evaluation of the Effect of D614G, N501Y and S477N Mutation in SARS-CoV-2 through Computational Approach

Sarmilah Mathavan, Suresh Kumar

Subject: Biology And Life Sciences, Virology Keywords: COVID-19; SARS-CoV-2; D614G; N501Y; S477N; mink; VOC 202012/01; B.1.1.7

Online: 28 December 2020 (17:00:23 CET)

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

Preprint ARTICLE | doi:10.20944/preprints202005.0113.v1

Prevalence of Current Smoking and Association with Adverse Outcome in Hospitalized COVID-19 Patients: A Systematic Review and Meta-Analysis

Konstantinos Farsalinos, Konstantinos Poulas, Riccardo Polosa, Anastasia Barbouni, Pasquale Caponnetto, Raymond Niaura

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: SARS-CoV-2; COVID-19; inflammation; smoking; nicotine; hospitalization; adverse outcome

Online: 7 May 2020 (08:52:04 CEST)

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Background: The purpose of this study was to examine the prevalence and effects of current smoking on adverse outcomes among hospitalized COVID-19 patients. Methods: We performed a systematic review of the literature (PubMed) for studies published until April 25. Studies were included into the analysis if they satisfied all of the following criteria: 1. To present hospitalized patients with COVID-19. 2. To classify patients into less and more severe disease, irrespective of the severity definition (defined as “adverse ourtcome”). 3. To present data on the smoking status, separately for each severity classification. We identified 18 (from a total of 1398) relevant studies. Pooled current smoking prevalence was compared with the gender-adjusted, population-based expected prevalence by calculating Prevalence Odds Ratio (POR). The association between current, compared to non-current and former, smoking and adverse outcome was examined by calculating Odds Ratio (OR). All analyses were performed using random-effects meta-analysis. Results: Among 6515 patients, 440 of whom were current smokers, the pooled prevalence of current smoking was 6.8% (95%CI: 4.8-9.1%) and the POR was 0.21 (95%CI: 0.16-0.26, P < 0.001). In Chinese studies only, the POR was 0.22 (95%CI: 0.17-0.27, P < 0.001). Current smokers were more likely to have an adverse outcome compared to non-current smokers (OR: 1.53, 95%CI: 1.06-2.20, P = 0.022). However, they were less likely to have an adverse outcome compared to former smokers (OR: 0.42, 95%CI: 0.27-0.74, P = 0.003). Conclusion: An unexpectedly low prevalence of current smoking was observed among hospitalized patients with COVID-19. Hospitalized current smokers had higher odds compared to non-current smokers but lower odds compared to former smokers for an adverse outcome. The possibility that nicotine may have a protective effect in COVID-19 which may be masked by smoking-related toxicity and by the abrupt cessation of nicotine intake when smokers are hospitalized should be explored.

Preprint REVIEW | doi:10.20944/preprints202003.0353.v1

In Search of Feasible Interventions for the Prevention and Cure of Novel Coronavirus Disease 2019

Sunil Kumar Verma

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: COVID-19; SARS-CoV-2; Severe Acute Respiratory Syndrome Coronavirus-2; Curcumin

Online: 24 March 2020 (03:16:22 CET)

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Preprint REVIEW | doi:10.20944/preprints202012.0242.v1

Long-Haul COVID-19: Putative Pathophysiology, Risk Factors, and Treatments

Shin Jie Yong

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: COVID-19; SARS-CoV-2; long-haul; inflammation; tissue damage; drug repurposing

Online: 10 December 2020 (09:42:20 CET)

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Working Paper REVIEW

Marine Red Alga Porphyridium sp. as a Source of Sulfated Polysaccharides (SPs) for Combating Against COVID-19

Vinod Nagle, Mahadev Gaikwad, Yogesh Pawar, Santanu Dasgupta

Subject: Biology And Life Sciences, Virology Keywords: Anti-viral; Carrageenan; Coronavirus; COVID-19; Porphyridium; sulfated polysaccharides (SPs)

Online: 10 April 2020 (07:49:11 CEST)

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Preprint BRIEF REPORT | doi:10.20944/preprints202005.0084.v1

Nsp7 and Spike Glycoprotein of SARS-CoV-2 Are Envisaged as Potential Targets of Vitamin D and Ivermectin

Jhimli Dasgupta, Udayaditya Sen, Abhisek Bakshi, Abhijit Dasgupta, Krishnendu Manna, Chinmay Saha, Rajat K. De, Satinath Mukhopadhyay, Nitai P. Bhattacharyya

Subject: Biology And Life Sciences, Virology Keywords: SARS-CoV-2; Vitamin D; Ivermectin; RNA-dependent-RNA polymerase; Spike glycoprotein; Knowledge based docking

Online: 5 May 2020 (15:18:30 CEST)

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COVID-19 has emerged as deadly pandemic worldwide with no vaccine or suitable antiviral drugs to prevent or cure the disease. Because of the time-consuming process to develop new vaccines or antiviral agents, there has been a growing interest in repurposing some existing drugs to combat SARS-CoV-2. Vitamin D is known to be protective against acute respiratory distress syndrome (ARDS), pneumonia and cytokine storm. Recently it has been used as a repurposed drug for the treatment of H5N1 virus-induced lung injury. Circumstantial evidences indicate that people with low level of vitamin D are more susceptible to SARS-CoV-2. Although, vitamin D was suggested to interfere with viral replication, its interaction with any SARS-CoV-2 protein is unexplored yet. Beside this, ivermectin, a well-known anti-parasitic agent, exhibits potent anti-viral activities in vitro against viruses such as HIV-1 and dengue. Very recently, ivermectin has been found to reduce viral load of SARS-CoV-2 in vitro. We have analyzed available structures of SARS-CoV-2 proteins to identify probable binding partner(s) of vitamin D and ivermectin through knowledge-based docking studies and figured out possible implication of their binding in SARS-CoV-2 infection. Our observations suggest that the non-structural protein nsp7 possesses a potential site to house 25-hydroxyvitamin D3 (VDY) or the active form of Vitamin D, calcitrol. Binding of vitamin D with nsp7 likely to hamper the formation of nsp7-nsp8 complex which is required to bind with RNA dependent RNA polymerase (RdRP), nsp12 for optimal function. On the other hand, potential binding site of ivermectin has been identified in the S2 subunit of trimeric spike(S) glycoprotein of SARS-CoV-2. We propose that deeply inserted mode of ivermectin binding at three inter-subunit junctions may restrict large scale conformational changes of S2 helices which is necessary for efficient fusion of viral and host membrane. Our study, therefore, opens up avenues for further investigations to consider vitamin D and ivermectin as potential drugs against SARS-CoV-2.

Preprint ARTICLE | doi:10.20944/preprints202002.0378.v3

Clinical, Laboratory and Imaging Features of COVID-19: A Systematic Review and Meta-analysis

Alfonso J. Rodriguez-Morales, Jaime A. Cardona-Ospina, Estefanía Gutiérrez-Ocampo, Rhuvi Villamizar-Peña, Yeimer Holguin-Rivera, Juan Pablo Escalera-Antezana, Lucia Elena Alvarado-Arnez, D. Katterine Bonilla-Aldana, Carlos Franco-Paredes, Andrés F. Henao-Martinez, Alberto Paniz-Mondolfi, Guillermo J. Lagos-Grisales, Eduardo Ramírez-Vallejo, Jose A. Suárez, Lysien I. Zambrano, Wilmer E. Villamil-Gómez, Graciela J. Balbin-Ramon, Ali A. Rabaan, Harapan Harapan, Kuldeep Dhama, Hiroshi Nishiura, Hiromitsu Kataoka, Tauseef Ahmad, Ranjit Sah

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: Coronavirus Disease 2019; SARS-CoV-2; clinical features; laboratory; outcomes; epidemic.

Online: 11 March 2020 (10:35:01 CET)

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Preprint REVIEW | doi:10.20944/preprints202004.0005.v1

SARS-CoV-2/COVID-19: Viral Genomics, Epidemiology, Vaccines, and Therapeutic Interventions

Mohammed Uddin, Farah Mustafa, Tahir A. Rizvi, Tom Loney, Hanan Al Suwaidi, Ahmad Al Marzouqi, Afaf Kamal Eldin, Nabeel Alsabeeha, Thomas E. Adrian, Cesare Stefanini, Norbert Nowotny, Alawi Alsheikh-Ali, Abiola C. Senok

Subject: Biology And Life Sciences, Virology Keywords: SARS-CoV-2; COVID-19; Coronavirus; Pandemic; Viral Genomics

Online: 1 April 2020 (09:22:38 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202003.0024.v1

Potential Inhibitors Targeting RNA-Dependent RNA Polymerase Activity (NSP12) of SARS-CoV-2

Zijing Ruan, Chao Liu, Yuting Guo, Zhenqing He, Xinhe Huang, Xu Jia, Tai Yang

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: SARS-CoV-2; nonstructural proteins (NSP); NSP12; NSP7; NSP8; virtual screening; inhibitor

Online: 2 March 2020 (03:11:33 CET)

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Preprint REVIEW | doi:10.20944/preprints202006.0007.v1

The Hype and Disruptive Technologies of Industry 4.0 in Major Industrial Sectors: A State of the Art

Ocident Bongomin

Subject: Engineering, Industrial And Manufacturing Engineering Keywords: 3D printing; Agriculture 4.0; Artificial of intelligence; Blockchain; Big Data; Coronavirus; Education 4.0; Energy 4.0; Finance 4.0; Globalization 4.0; Healthcare 4.0; Industry 4.0 technologies; Internet of Things; Learning Factory; Logistic 4.0

Online: 2 June 2020 (15:02:07 CEST)

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Preprint REVIEW | doi:10.20944/preprints202007.0681.v1

Asymptomatic COVID-19; We Don’t Know What We Don’t Know

Olen R. Brown

Subject: Social Sciences, Government Keywords: asymptomatic disease; communicability; COVID-19; death rate; Ro; SARS-CoV-2; social distancing; transmission rate; infection rate; quarantine

Online: 28 July 2020 (11:57:26 CEST)

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

Working Paper CASE REPORT

SARS-CoV-2 Infection in the Central Nervous System of a 1-Year-Old Infant

Ismael Carlos Gomes, Karina Karmirian, Julia Oliveira, Carolina Pedrosa, Mayara Abud Mendes, Fernando Colonna Rosman, Leila Chimelli, Stevens Rehen

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: SARS-CoV-2 neuroinvasion; COVID-19; infant; Choroid plexus

Online: 15 March 2021 (13:03:33 CET)

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Preprint REVIEW | doi:10.20944/preprints202010.0407.v2

Vitamin C—An Adjunctive Therapy for Respiratory Infection, Sepsis and COVID-19

Patrick Holford, Anitra Carr, Thomas H. Jovic, Stephen R. Ali, Iain S. Whitaker, Paul Marik, David Smith

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: COVID-19; SARS-CoV-2; coronavirus; vitamin C; ascorbate; colds; pneumonia; sepsis; immunonutrition; supplementation

Online: 30 November 2020 (15:23:16 CET)

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Preprint REVIEW | doi:10.20944/preprints202005.0160.v1

COVID-19 and Kawasaki Like Disease: The Known-Known, the Unknown-Known and the Unknown-Unknown

Aurélie Morand, Diego Urbina, Alexandre Fabre

Subject: Medicine And Pharmacology, Pediatrics, Perinatology And Child Health Keywords: Sars-Cov2; Covid-19; Children; Kawasaki disease; toxic shock syndrome

Online: 9 May 2020 (09:01:24 CEST)

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

Preprint ARTICLE | doi:10.20944/preprints202104.0034.v5

SARS-CoV2 Variants and Vaccines mRNA Spikes Fibonacci Numerical UA/CG Metastructures

Jean-Claude Perez

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: SARS-CoV2; Biomathematics; vaccine; variants; mRNA; Fibonacci; numerical standing waves

Online: 20 April 2021 (10:05:55 CEST)

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ABSTRACT. In this paper, we suggest a biomathematical numerical method for analysing mRNA nucleotides sequences based on UA/CG Fibonacci numbers proportions. This method is used to evaluate then compare the spike genes related to the main SARS-CoV2 VARIANTS currently circulating within the world population. The 10 main results proposed to be reproduced by peers are: 1/ SARS-CoV2 genome and spike evolution in one year 2020-2021. 2/ SARS-CoV2 Origins. 3/ Comparing 11 reference variants spikes. 4/ analysing 32 CAL.20C California variant patients spikes. 5/ Toward a meta mRNA Fibonacci gene end message code. 6/ Analysing S501 UK, S484 South Africa and « 2 mutations » INDIA variants. 7/ Suggesting a possible variants spike mRNA palindrome symmetry metastructure improving mRNA stability then infectiousness. 8/ Analysing Fibonacci Metastructures in the mRNA coding for the vaccines PFIZER and MODERNA. 9/ Does the CG-rich modification of the synonymous codons of the spikes of the 2 mRNA vaccines affect the expression and quantity of SARS-CoV2 antibodies? 10/ The exceptional case of the Brazilian variant P.1. Particularly, we suggest the following conjecture at mRNA folding level : CONJECTURE of SARS-CoV2 VARIANTS: The growth of long Fibonacci structures in the shape of "podiums" for almost all of the variants studied (UK, California, South Africa, India, etc.) suggests the probable folding of the Spike mRNA in the form of a "hairpin", which can strengthen the cohesion and the lifespan of this mRNA. Finally, we show that these kinds of Fibonacci matastructures disapear TOTALLY by analysing the published mRNA sequences of PFIZER and MODERNA vaccines. One fact is certain, the two mRNAs of the Moderna and Pfizer vaccines will result in a low functionality of the spike vaccine. This is because their designers by seeking greater stability, have doped to build CG rich sequences which, as soon as they are inserted into the human host, will, paradoxically, seek to mutate, like SARS-CoV2 variants, towards CG ==> UA forms in order to improve their STABILITY and LIFETIME. We conclude using new biomathematics theoretical methods (Master code and numerical standing waves), and comparing the Spikes of the two vaccines Moderna and Pfizer, that there will be very probable differences in stability and shelf life of the two respective mRNAs vaccines. However, “State of the Art” analyzes will disclose that their two protein sequences are strictly identical. By modified their synonymous codons using different strategies, no one can guarantee that the quantity of antibodies generated will be identical in the two cases. We wish to draw attention to the great ADAPTATION power - at the global scale of their genomes - of the most infectious VARIANTS, such as the BRAZIL 20J / 501Y.V3 variant (P.1). This is very worrying for the VACCINES <==> VARIANTS run: We demonstrate how the Brazilian variant P.1 which becomes uncontrollable in Brazil in April 2021 has a level of organization of long metastructures of 17,711 bases covering the genome which is 3.6 more important than that of the 2 reference genomes SARS-CoV2 and worldwide D614G. We suggest that this high level of overall structure of this variant contributes to the stability of this genome and, might explain its greater contagiousness.

Preprint ARTICLE | doi:10.20944/preprints202002.0307.v1

Bioinformatic Analysis Reveals That the Reproductive System is Potentially at Risk from SARS-CoV-2

Jiawei Zhang, Yuqi Wu, Rui Wang, Keshi Lu, Menjiang Tu, Huan Guo, Weijie Xie, Zizhen Qin, Shulin Li, Pei Zhu, Xiangwei Wang

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: SARS-CoV-2; ACE2; reproductive system; single-cell RNA-seq

Online: 21 February 2020 (08:09:25 CET)

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Preprint REVIEW | doi:10.20944/preprints202009.0153.v1

Viruses, Vaccines and the Race for a Covid-19 Vaccine: A Tutorial

Subramani Mani

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: Virus; Vaccine; SARS-CoV-2; Coronavirus; Covid-19; Covid-19 vaccine

Online: 7 September 2020 (03:46:59 CEST)

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Working Paper BRIEF REPORT

Exploring Potential Super Infection in SARS-CoV2 by Genome-Wide Analysis and Receptor–Ligand Docking

Chuanjun Shu, Xuan Huang, Juergen Brosius, Cheng Deng

Subject: Biology And Life Sciences, Cell And Developmental Biology Keywords: SARS-CoV2; spike; receptor–ligand docking; super infection

Online: 20 March 2020 (08:30:40 CET)

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Preprint ARTICLE | doi:10.20944/preprints202004.0316.v2

Early Crop-Type Mapping Under Climate Anomalies

Michael Marszalek, Maximilian Lösch, Marco Körner, Urs Schmidhalter

Subject: Environmental And Earth Sciences, Environmental Science Keywords: Precision farming; Early crop-type mapping; Sentinel-2; Random Forest; SVM

Online: 17 January 2022 (10:54:10 CET)

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Preprint ARTICLE | doi:10.20944/preprints202003.0291.v1

Co-infection of Coronavirus Disease 2019 and Influenza: A Report from Iran

Zohre Khodamoradi, Mohsen Moghadami, Mehrzad Lotfi

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: co-infection; coronavirus disease 2019; COVID-19; influenza

Online: 19 March 2020 (02:00:47 CET)

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Preprint REVIEW | doi:10.20944/preprints202002.0399.v1

Preliminary Case Report on the SARS-CoV-2 Cluster in the UK, France, and Spain

Emma B. Hodcroft

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: COVID-19 SARS-CoV-2 hCOV-19 coronavirus epidemiology contact-tracing cluster outbreak epidemic

Online: 27 February 2020 (11:08:56 CET)

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Preprint COMMUNICATION | doi:10.20944/preprints202004.0093.v2

Bioaerosol Size Effect in COVID-19 Transmission

Marcelo I. Guzman

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: COVID-19; SARS-CoV-2; virus, bioaerosol; social distancing; aerodynamic size; infection

Online: 22 April 2020 (05:54:48 CEST)

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Preprint REVIEW | doi:10.20944/preprints202004.0155.v1

COVID-19 Testing: Challenges, Limitations and Suggestions for Improvement

Emily Hu

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: COVID-19; Coronavirus; False-negative; Nucleic Acid Test; Screening; Diagnostic Accuracy; Missed Diagnosis; Epidemic; Infectious Disease

Online: 9 April 2020 (14:37:56 CEST)

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Preprint REVIEW | doi:10.20944/preprints202004.0091.v1

COVID-19: A Review on Molecular Basis, Pathogenic Mechanisms, Therapeutic Aspects and Future Projections

Muneeb Faiq, Ashutosh Kumar, Himanshu Singh, Vikas Pareek, Rizwana Qadri, Khursheed Raza, Chiman Kumari, Ravi Narayan, Pavan Kumar, Maheswari Kulandhasamy, Sada Pandey

Subject: Biology And Life Sciences, Virology Keywords: Coronavirus; Pneumonia; COVID-19; Virus; Flu; Vaccine; Epidemic; Pandemic

Online: 7 April 2020 (11:15:55 CEST)

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Preprint ARTICLE | doi:10.3390/sci2040077

Atmospheric Temperature and CO<sub>2</sub>: Hen-or-Egg Causality?

Demetris Koutsoyiannis, Zbigniew Kundzewicz

Subject: Environmental And Earth Sciences, Environmental Science Keywords: temperature; global warming; greenhouse gases; atmospheric CO₂ concentration

Online: 20 October 2020 (00:00:00 CEST)

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Preprint BRIEF REPORT | doi:10.20944/preprints202004.0024.v1

Emergence of Drift Variants That May Affect COVID-19 Vaccine Development and Antibody Treatment

Takahiko Koyama, Dilhan Weeraratne, Jane L. Snowdon, Laxmi Parida

Subject: Biology And Life Sciences, Virology Keywords: COVID-19; SARS-nCoV-2; vaccine; antibody; immune escape; variant; spike protein; genomic drift; convalescent plasma

Online: 3 April 2020 (04:24:52 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202004.0512.v6

The Structure of the Membrane Protein of SARS-CoV-2 Resembles the Sugar Transporter semiSWEET

Sunil Thomas

Subject: Biology And Life Sciences, Virology Keywords: SARS-CoV-2; COVID-19; Coronavirus; Virus; sugar transporter; SemiSWEET; Membrane glycoprotein, Pandemic

Online: 19 October 2020 (10:48:05 CEST)

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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.

Preprint REVIEW | doi:10.20944/preprints202003.0343.v1

Emerging Coronavirus Disease (COVID-19), a Pandemic Public Health Emergency with Animal Linkages: Current Status Update

Yashpal Singh Malik, Shubhankar Sircar, Sudipta Bhat, Obli Rajendran Vinodhkumar, Ruchi Tiwari, Ranjit Sah, Ali A. Rabaan, Alfonso J. Rodriguez-Morales, Kuldeep Dhama

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: coronavirus; 2019-nCoV; SARS-CoV-2; animal coronaviruses; COVID-19; bat coronavirus; zoonoses; epidemiology; transmission; diagnosis; antivirals; prevention and control

Online: 23 March 2020 (07:19:35 CET)

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

Preprint ARTICLE | doi:10.20944/preprints202003.0085.v1

Structural Elucidation of SARS-CoV-2 Vital Proteins: Computational Methods Reveal Potential Drug Candidates Against Main Protease, Nsp12 RNA-dependent RNA Polymerase and Nsp13 Helicase

Muhammad Usman Mirza, Matheus Froeyen

Subject: Biology And Life Sciences, Virology Keywords: SARS-CoV-2; COVID-19; CoV-Mpro; CoV-Nsp12 polymerase; CoV-Nsp13 helicase

Online: 5 March 2020 (11:50:45 CET)

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Preprint ARTICLE | doi:10.20944/preprints202008.0220.v1

The PHA4GE SARS-CoV-2 Contextual Data Specification for Open Genomic Epidemiology

Emma J. Griffiths, Ruth E. Timme, Andrew J. Page, Nabil-Fareed Alikhan, Dan Fornika, Finlay Maguire, Catarina Inês Mendes, Simon H. Tausch, Allison Black, Thomas R. Connor, Gregory H. Tyson, David M. Aanensen, Brian Alcock, Josefina Campos, Alan Christoffels, Anders Gonçalves da Silva, Emma Hodcroft, William W.L. Hsiao, Lee S. Katz, Samuel M. Nicholls, Paul E. Oluniyi, Idowu B. Olawoye, Amogelang R. Raphenya, Ana Tereza R. Vasconcelos, Adam A. Witney, Duncan R. MacCannell

Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: genomics; metadata; SARS-CoV-2; bioinformatics; data standards

Online: 9 August 2020 (15:53:58 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202004.0337.v1

Reporting Two SARS-CoV-2 Strains Based on A Unique Trinucleotide-Bloc Mutation and Their Potential Pathogenic Difference

Mustak Ibn Ayub

Subject: Biology And Life Sciences, Virology Keywords: SARS-CoV-2; COVID-19; strains of SARS-CoV-2

Online: 19 April 2020 (07:14:52 CEST)

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

Preprint REVIEW | doi:10.20944/preprints202007.0108.v1

COVID-19: Comprehensive Synopsis of Suggested Pathophysiological Mechanisms and Repurposed Drugs

Mathijs Binkhorst, Annette K. Offringa, Johannes G. van der Hoeven

Subject: Medicine And Pharmacology, Pharmacy Keywords: COVID-19; SARS-CoV-2; coronavirus; hypothesis; pathophysiology; drug repurposing

Online: 7 July 2020 (02:50:55 CEST)

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Preprint REVIEW | doi:10.20944/preprints202004.0040.v3

COVID-19 Virus Infection and Transmission are Observably Less in Highly Dengue-endemic Countries: Can Dengue Vaccines be “Repurposed” to Prevent COVID-19?

Subhajit Biswas, Soumi Sukla

Subject: Biology And Life Sciences, Virology Keywords: Dengue; COVID-19; SARS-CoV-2; epidemiology; infection; mortality; cross-protection; Dengue vaccine; ELISA; Dengvaxia

Online: 5 May 2020 (03:00:34 CEST)

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Preprint HYPOTHESIS | doi:10.20944/preprints202003.0428.v1

A Furin Cleavage Site Inserted into the Spike Protein of SARS-CoV-2: A Structural Implication?

Wei Li

Subject: Biology And Life Sciences, Biophysics Keywords: COVID-19; SARS-CoV-2; furin cleavage site (FCS); salt bridging analysis

Online: 29 March 2020 (08:54:42 CEST)

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Working Paper ARTICLE

Complementary Application of the Ozonized Saline Solution in Mild and Severe Patients with Pneumonia Covid-19: A Non-randomized Pilot Study

Adriana Schwartz, Gregorio Martínez-Sánchez, Alejandra Menassa de Lucía, Sergio Mejía Viana, Constanta Alina Mita

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: ozone therapy; ozonized saline solution; SARS-CoV-2; COVID-19; pneumonia

Online: 12 July 2020 (16:30:51 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202003.0286.v1

Network Bioinformatics Analysis Provides Insight into Drug Repurposing for COVID-2019

Xu Li, Jinchao Yu, Zhiming Zhang, Jing Ren, Alex E. Peluffo, Wen Zhang, Yujie Zhao, Kaijing Yan, Daniel Cohen, Wenjia Wang

Subject: Medicine And Pharmacology, Pharmacy Keywords: COVID-2019; SARS-CoV-2; repurposing; network bioinformatics

Online: 18 March 2020 (08:50:10 CET)

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Working Paper REVIEW

SARS-CoV-2 Vaccines: ‘Warp Speed’ Needs Mind Melds not Warped Minds

John P. Moore, P. J. Klasse

Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: SARS-CoV-2; S-protein; RBD; COVID-19; neutralizing antibodies; serology; vaccines; animal models; Warp Speed

Online: 21 June 2020 (15:44:06 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202004.0140.v1

A Mathematical Model of COVID-19 Using Fractional Derivative: Outbreak in India with Dynamics of Transmission and Control

Amjad S. Shaikh, Iqbal N. Shaikh, Kottakkaran Sooppy Nisar

Subject: Computer Science And Mathematics, Analysis Keywords: mathematical models; coronavirus; caputo-fabrizio derivative; basic reproduction number; existence and stability; numerical simulations

Online: 9 April 2020 (08:12:53 CEST)

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Working Paper CONCEPT PAPER

Public Use of Masks to Control the Coronavirus Pandemic

Nicholas R. Longrich, Samuel K. Sheppard

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: COVID-19; face masks; epidemiology; coronavirus; pandemics

Online: 12 April 2020 (08:41:58 CEST)

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

Preprint HYPOTHESIS | doi:10.20944/preprints202004.0269.v1

Antibiotics Against COVID-19 and Mitochondria? Urgent Thinking Out of the Box

Jaroslaw Tyszka, Karolina Kobos, Aleksandra Tyszka

Subject: Chemistry And Materials Science, Theoretical Chemistry Keywords: COVID-19; SARS-CoV-2; pandemic; antibiotics; immune response; mitochondria; epidemiology; health policy

Online: 16 April 2020 (12:14:30 CEST)

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Italian, Spanish, French vs German, Austrian or Norwegian COVID-19 tracks? Antibiotics might have a partial impact on COVID-19 death rates in various countries. Our working hypotheses based on recent publications is that that antibiotics may be a major factor that negatively affects patients’ immune system during viral infections. We are all aware that there is no specific and effective medical treatment for COVID-19 so far. However, we know that our immune system is the only efficient weapon that fights against this syndrome right now. In fact, antibiotics are very often prescribed to prevent secondary infections following an antiviral immune response. Various antibiotic therapies have also been commonly applied to support COVID-19 treatments in China and Italy. Unfortunately, the frequent antibiotic off-site targets include mitochondria that are genetically and evolutionary closely linked to bacteria. Mitochondria are multifunctional organelles responsible for bioenergetics in nearly all our cells, acting as signaling hubs in antiviral and antibacterial immune responses. Several studies have demonstrated that mitochondria are vulnerable to antibacterial treatments, interrupting their physiology. Inhibition of these processes by antibiotics might render the immune system less capable of fighting acute COVID-19 viral infections. Some antibiotics, including those prescribed for COVID-19 in Wuhan, have been shown to inhibit the synthesis of mitochondrial DNA. The question is whether antibiotics support such a treatment or weaken patient immune responses in this case. This hypothesis should be evaluated based on comparative clinical data that seem to be unavailable at the moment. Possibly the COVID-19 risk group should be extended to all patients being treated with antibiotics, including those who finished antibiotic therapies days up to several months before SARS-CoV-2 infection. We therefore urge health service response groups to evaluate the impact of antibiotics on COVID-19 recovery vs death retrospective data. We would like to motivate international, national and local health authorities to share available clinical treatment data, discuss and optimize treatment strategies.

Preprint REVIEW | doi:10.20944/preprints202005.0060.v3

Fighting the SARS CoV-2 (COVID-19) Pandemic with Soap

Narendra Kumar Chaudhary, Nabina Chaudhary, Manis Dahal, Biswash Guragain, Sumie Rai, Rahul Chaudhary, K.M. Sachin, Reena Lamichhane-Khadka, Ajaya Bhattarai

Subject: Chemistry And Materials Science, Analytical Chemistry Keywords: COVID-19; SARS-Cov-2; soap; hand washing; WHO

Online: 6 July 2021 (11:30:53 CEST)

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Preprint REVIEW | doi:10.20944/preprints202004.0417.v1

Acute Care Physiotherapy Management of COVID-19 Patients in Qatar: Best Practice Recommendations

Ajimsha MS, Neeraj Gampawar, Praveen Surendran, Prasobh Jacob, Vasileios Karpouzis, Mohamed Haneef, Muhamed Aleef, Shameem Ali, Reshma Praveen, Eladel Bouguerra, Noora Almudahka

Subject: Public Health And Healthcare, Nursing Keywords: Coronavirus; COVID-19; SARS-Cov-2; infection; Physiotherapy; rehabilitation

Online: 23 April 2020 (15:22:55 CEST)

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Preprint HYPOTHESIS | doi:10.20944/preprints202002.0254.v2

Discovery of Anti-2019-nCoV Agents from 38 Chinese Patent Drugs toward Respiratory Diseases via Docking Screening

Yong-Ming Yan, Xin Shen, Yong-Kai Cao, Jiao-Jiao Zhang, Yan Wang, Yong-Xian Cheng

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: 2019-nCoV; novel coronavirus pneumonia; docking; ACE2; viral main protease

Online: 23 February 2020 (02:09:52 CET)

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Preprint ARTICLE | doi:10.20944/preprints202009.0327.v1

Transmission of SARS-CoV-2 in Northern Ghana; Insights from Whole Genome Sequencing

Augustina Angelina Sylverken, Philip El-Duah, Michael Owusu, Julia Schneider, Richmond Yeboah, Ayisi-Boateng Ayisi-Boateng, Richmond Gorman, Eric Adu, Alexander Kwarteng, Michael Frimpong, Sherihane Aryeetey, Jesse Addo Asamoah, Yaw Ampem Amoako, John Humphrey Amuasi, Jörn Beheim-Schwarzbach, Ellis Owusu-Dabo, Yaw Adu-Sarkodie, Kwasi Obiri-Danso, Victor Max Corman, Christian Drosten, Richard Phillips

Subject: Biology And Life Sciences, Virology Keywords: Ghana; SARS-CoV-2; transmission; Phylogenetics

Online: 15 September 2020 (04:24:17 CEST)

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In regions lacking genomic data, analysis of sequences from the early stages of an outbreak can provide important insights into the diversity of pathogens present. Following the detection of the first imported case of COVID-19 in the Northern sector of Ghana on 13^th March 2020, we have now molecularly characterized and phylogenetically analysed sequences including three (3) complete genomes of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) isolated from nine (9) patients observed in Ghana. Eight (8) of these patients reported with a recent history of foreign travel and one (1) with no history of foreign travel. We performed high throughput sequencing for 9 samples following the determination of high concentration of viral RNA. In addition, we estimated the potential impact that long distance transportation of samples to testing centres may have on sequencing outcomes. Here, two samples that were closest in terms of viral RNA concentration but transported from sites which are over 400km apart were assessed. All sequences were compared to previous sequences from Ghana and representative sequences from regions where our patients had previously travelled. Complete genomes were obtained for three (3) sequences and with another near complete genome with a coverage of 95.6%. Sequences with coverage in excess of 80% were found to belong to three lineages namely A, B.1 and B.2. Our sequences clustered in two different clades with the majority falling within a clade composed of sequences from sub-Saharan Africa. Less RNA fragmentation was seen in sample KATH23 which was collected 9km compared with sample TTH6 which was collected and transported over a distance of 400km to the testing site. The clustering of several sequences from sub-Saharan Africa suggests regional circulation of the viruses in the subregion. Importantly, there may be the need to decentralize testing sites and build more capacity across Africa to boost the sequencing output of the subregion.

Preprint ARTICLE | doi:10.20944/preprints202005.0413.v1

Characterization of Nucleocapsid (N) Protein from Novel Coronavirus SARS-CoV-2

Abhishek Kumar, Alisha Parveen, Narendra Kumar, Sneha Bairy, Vibha Kaushik, Chetan Chandola, Jyoti Sharma, Phulwanti Sharma, Akhil Agarwal, Akhilesh Pandey, Pankaj Goyal, Muniasamy Neerathilingam

Subject: Biology And Life Sciences, Virology Keywords: SARS-CoV-2; nucleocapsid (N); genomics; coronavirus; Wuhan; Pandemic

Online: 25 May 2020 (17:45:40 CEST)

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Preprint CASE REPORT | doi:10.20944/preprints202004.0384.v1

Tackling the Pandemic COVID-19: The Bangladesh Perspective

Md. Taimur Islam, Anup Kumar Talukder, Md. Nurealam Siddiqui, Tofazzal Islam

Subject: Biology And Life Sciences, Virology Keywords: SARS-CoV-2; COVID-19; Bangladesh; Pandemic; stimulus package

Online: 21 April 2020 (09:34:19 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202004.0068.v2

Discovery of Multi-Target-Directed Ligands by Targeting Host-specific SARS-CoV-2’s Structurally Conserved Main Protease

Rakesh Joshi, Shounak Jagdale, Sneha Bansode, S. Shiva Shankar, Meenakshi Tellis, Vaibhav Kumar Pandya, Ashok Giri, Mahesh Kulkarni

Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: coronavirus; COVID-19; hACE-2; MPro; multi-target-directed ligand; protease inhibito; RdRp; SARS-CoV-2 virus

Online: 9 April 2020 (05:13:05 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202005.0015.v1

COVID-19 Public Sentiment Insights and Machine Learning for Tweets Classification

Jim Samuel, G. G. Md. Nawaz Ali, Md. Mokhlesur Rahman, Ek Esawi, Yana Samuel

Subject: Computer Science And Mathematics, Information Systems Keywords: COVID-19; coronavirus; machine learning; sentiment analysis; textual analytics; Twitter

Online: 2 May 2020 (13:52:28 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202002.0308.v1

Pharmacoinformatics and Molecular Dynamic Simulation Studies Reveal Potential Inhibitors of SARS-CoV-2 Main Protease 3CL^pro

Mubarak A. Alamri, Muhammad Tahir ul Qamar, Safar M. Alqahtani

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: SARS-CoV-2; COVID-19; 3CL protease; molecular docking; molecular dynamics and simulations

Online: 23 February 2020 (02:17:46 CET)

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Preprint REVIEW | doi:10.20944/preprints202004.0234.v1

Compounding Health Risks and Increased Vulnerability to SARS-CoV-2 for Racial and Ethnic Minorities and Low Socioeconomic Status Individuals in the United States

Elise M. Myers

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: coronavirus; COVID-19; comorbidity; race and ethnicity; health disparities; income; inequality; influenza

Online: 15 April 2020 (09:25:47 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202004.0334.v1

Molecular Docking and Molecular Dynamic Study of Two Viral Proteins Associated with SARS-CoV-2 with Ivermectin

Lenin Andres Gonzalez Paz, Carla A. Lossada, Luis S. Moncayo, Freddy Romero, J. L. Paz, Joan Vera-Villalobos, Aleivi E. Perez, Ernesto San-Blas, Ysaias J. Alvarado

Subject: Chemistry And Materials Science, Medicinal Chemistry Keywords: SARS-COV-2; folding/unfolding; antiparasitic; molecular docking; molecular dynamics; COVID-19; Ivermectin

Online: 19 April 2020 (06:56:09 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202206.0192.v1

Implementation of the eCDC/WHO Recommendation for Molecular Diagnosis of SARS-CoV-2 Omicron Subvariants and Its Challenges

Sin Hang Lee

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: eCDC; WHO; Sanger sequencing; Omicron variant; minor subvariants; BA.4/BA.5; BA.2; mul-ti-allelic; SNPs; recombinant

Online: 14 June 2022 (04:30:41 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202009.0375.v1

Unexpected Co-infection with Different Strains of SARS-CoV-2 in Patients with COVID-19

Hayder O. Hashim, Mudher K. Mohammed, Mazin J. Mousa, Hadeer H. Abdulameer, Alaa T.S. Alhassnawi, Safa A. Hassan, Mohammed Baqur S. Al-Shuhaib

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: co-infection; SARS-CoV-2; pike glycoprotein; stop mutations

Online: 17 September 2020 (05:33:59 CEST)

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There is a rising global concern for the ongoing outbreak of SARS-CoV-2 due to its high transmission rate and unavailability of treatment. Through the binding of its spike glycoprotein with angiotensin type 2 (ACE2), SARS-CoV-2 can efficiently get in the cells of patients and start its pandemic cycle. Herein, the biological diversity of SARS-CoV-2 infection was assessed in Babylon province of Iraq by investigating the possible genetic variations of the spike glycoprotein. A specific coding region of 795 bp within the viral spike (S) gene was amplified from 19 patients who suffered from obvious symptoms of SARS-CoV-2 infection. Sequencing results identified fifteen novel nucleic acid variations with a variety of distributions within the investigated samples. The electropherograms of all the identified variations showed obvious co-infections with at least two different viral strains per sample. Within these co-infections, the majority of samples exhibited three nonsense single nucleotide polymorphism (SNP)s, p.301Cdel, p.380Ydel, and p.436del, which yielded three truncated SARS-CoV-2 spike glycoproteins of 301, 380, and 436 amino acids length, respectively. The network and phylogenetic analyses indicated that for all viral infections were derived from multi-ancestral origins. Results inferred from the specific clade-based tree entailed that some viral strains were derived from European G-clade sequences. In conclusion, our data demonstrated the absence of any single strain infection among all investigated viral samples in the studied area, which may entail a higher risk of SARS-CoV-2 in this country. Through the identified high frequency of truncated spike proteins, we suggest that defective SARS-CoV-2 may depend on helper strains having intact spikes in its infection. Alternatively, another putative ACE2-independent route of viral infection way also suggested. To the best of our knowledge, this is the first report to describe the co-infection of multiple strains of SARS-CoV-2 in patients with COVID-19.

Preprint SHORT NOTE | doi:10.20944/preprints202008.0205.v3

The Anomalous Nature of the Fecal Swab Data, Receptor Binding Domain and Other Questions in RaTG13 Genome

Monali Rahalkar, Rahul Bahulikar

Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: RaTG13; SARS-COV-2; Illumina sequencing, amplicon sequencing, NGS; fecal swab

Online: 5 October 2020 (12:20:17 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202002.0385.v1

Rapid Design of a Bait Capture Platform for Culture- and Amplification-Free Next-Generation Sequencing of SARS-CoV-2

Jalees A. Nasir, David J. Speicher, Robert A. Kozak, Hendrik N. Poinar, Matthew S. Miller, Andrew G. McArthur

Subject: Biology And Life Sciences, Virology Keywords: Coronavirus; SARS-CoV-2; enrichment; next-generation sequencing

Online: 26 February 2020 (02:27:21 CET)

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Preprint HYPOTHESIS | doi:10.20944/preprints202002.0147.v4

The clinically validated viral superinfection therapy (SIT) platform technology could cure early cases of COVID-19 disease

Imre Kovesdi, Volker Sandig, Shimon Slavin, Wolfgang Renz, Marc Van Ranst, Peter M. Chumakov, Tibor Bakács

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Coronavirus; SARS-CoV-2; COVID-19; interferon; IFN; superinfection therapy; SIT; infectious bursal disease virus; IBDV; R903/78; safety; treatment

Online: 1 February 2021 (16:07:55 CET)

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Preprint ARTICLE | doi:10.20944/preprints202006.0293.v1

Doxycycline and Pentoxifylline for Mild and Mild-To-Moderate Covid-19

Emil Toma

Subject: Biology And Life Sciences, Virology Keywords: Covid-19; SARS-CoV-2; doxycycline; pentoxifylline; treatment; proposal

Online: 24 June 2020 (09:47:14 CEST)

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Preprint REVIEW | doi:10.20944/preprints202004.0321.v1

Plants as a Prospective Source of Natural Anti-viral Compounds and Oral Vaccines Against COVID-19 Coronavirus

Mahdi Yonesi, Alireza Rezazadeh

Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: 2019 Novel Coronavirus; plants; antiviral compounds; plant recombinant vaccines

Online: 19 April 2020 (04:15:18 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202205.0415.v1

Knowledge Levels of Acceptance and Hesitancy of COVID-19 Vaccine Among General Population of the Kingdom of Saudi Arabia

Adi Essam Zarei, Bayan Sajer, Feda Alharshani, Afrah Alshehri, Lamar Faidah, Wafa Alshehri

Subject: Public Health And Healthcare, Public Health And Health Services Keywords: COVID-19; Coronavirus; Vaccine hesitancy; COVID-19 Vaccine; Saudi Arabia

Online: 31 May 2022 (09:22:49 CEST)

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Preprint HYPOTHESIS | doi:10.20944/preprints202003.0042.v2

Virtual Screening of Inhibitors Against Spike Glycoprotein of SARS-CoV-2: A Drug Repurposing Approach

Kanishka Senathilake, Sameera Samarakoon, Kamani Tennekoon

Subject: Biology And Life Sciences, Virology Keywords: Flue; Virus; COVID19; SARS CoV-2; Spike Protein; Virtual Screening; dgitoxin; anthracycline; rolitetracycline; E-155

Online: 23 March 2020 (10:19:17 CET)

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Preprint ARTICLE | doi:10.20944/preprints202002.0447.v1

An Evolutionary RGD Motif in the Spike Protein of SARS-CoV-2 may Serve as a Potential High Risk Factor for Virus Infection?

Shijia Yan, Haixia Sun, Xianzhang Bu, Guohui Wan

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: SARS-CoV-2; ACE2; RGD; Spike protein; therapeutic drugs

Online: 28 February 2020 (16:26:53 CET)

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Working Paper ARTICLE

The INDIA Mutations and B.1.617 Variants: Is there a Global "Strategy" for Mutations and Evolution of Variants of the SARS-CoV2 Genome?

Jean-claude Perez

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: SARS-CoV2; Biomathematics; vaccine; variants; mRNA; Fibonacci; Indian variants; B.1.617; B.1.617.2.

Online: 18 May 2021 (14:05:33 CEST)

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Preprint REVIEW | doi:10.20944/preprints202012.0717.v1

COVID-19 Vaccine Hesitancy Worldwide: A Systematic Review of Vaccine Acceptance Rates

Malik Sallam

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: vaccine hesitancy; vaccine acceptance; anti-vaccination; COVID-19; coronavirus; SARS-CoV-2; vaccine rejection

Online: 29 December 2020 (08:46:16 CET)

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Preprint REVIEW | doi:10.20944/preprints202006.0132.v1

A Brief Review of Materials and Designs for Homemade Masks to Protect Against COVID-19

Jago Strong-Wright

Subject: Chemistry And Materials Science, Materials Science And Technology Keywords: COVID-19; SARS-CoV-2; masks materials; pandemic

Online: 11 June 2020 (11:44:17 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202105.0474.v1

Socioeconomic Inequalities in COVID-19 Confirmed Infection Across Three Waves. A Multilevel Approach in a Southern European Region

Isabel Aguilar-Palacio, Lina Maldonado, Sara Malo, Raquel Sánchez-Recio, Iván Marcos-Campos, Rosa Magallón-Botaya, MªJosé Rabanaque

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: COVID-19; coronavirus infection; inequalities; socioeconomic factors.

Online: 20 May 2021 (10:21:34 CEST)

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Preprint REVIEW | doi:10.20944/preprints202004.0011.v1

SARS-CoV-2: Jumping the Species Barrier, Lessons from SARS and MERS, Its Zoonotic Spillover, Transmission to Humans, Preventive and Control Measures and Recent Developments to Counter This Pandemic Virus

Kuldeep Dhama, Shailesh Kumar Patel, Khan Sharun, Mamta Pathak, Ruchi Tiwari, Mohd. Iqbal Yatoo, Yashpal Singh Malik, Ranjit Sah, Ali A. Rabaan, Parmod Kumar Panwar, Karam Pal Singh, Izabela Michalak, Wanpen Chaicumpa, D. Katterine Bonilla-Aldana, Alfonso J. Rodriguez-Morales

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: COVID-19; SARS-Cov-2; bat coronavirus; zoonosis; spillover; expanding host range

Online: 2 April 2020 (04:43:45 CEST)

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Working Paper HYPOTHESIS

Could Protein Malnutrition of Rapid Onset Explain the Atypical Symptoms of COVID-19 and Consequential Malfunctioning of the Body? A Hypothesis.

Maralyn Green

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: malnutrition; COVID-19; protein; immune system; SARS-CoV-2; cell proliferation; starvation

Online: 22 September 2020 (08:32:14 CEST)

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Working Paper ARTICLE

COVID-19: Pediatric Oral Health During and After the Pandemics

Valeria Luzzi, Gaetano Ierardo, Maurizio Bossù, Antonella Polimeni

Subject: Medicine And Pharmacology, Dentistry And Oral Surgery Keywords: COVID-19; pandemics; pediatric dentistry; oral health prevention; coronavirus

Online: 16 May 2020 (18:11:49 CEST)

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Preprint CONCEPT PAPER | doi:10.20944/preprints202005.0097.v5

Why Blood Group A Individuals Are at Risk Whereas Blood Group O Individuals Might Be Protected from SARS-CoV-2 (COVID-19) Infection: A Hypothesis Regarding How the Virus Invades the Human Body via Abo(H) Blood Group-Determining Carbohydrates

Peter Arend

Subject: Biology And Life Sciences, Virology Keywords: COVID-19; SARS-CoV-2–human carbohydrate interaction; trans-species glycosylation; A-like/Tn structure; trans-species glycan bridge

Online: 13 November 2020 (09:42:18 CET)

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Preprint REVIEW | doi:10.20944/preprints202005.0070.v2

Possible Effects of Air Temperature on COVID-19 Disease Severity and Transmission Rates

Dominique Kang, Clifford Ellgen, Erik Kulstad

Subject: Biology And Life Sciences, Virology Keywords: Covid; covid-19; sars-cov-2; temperature; heat; body temperature; air temperature; viral decay; viral stability; transmission; severity; virology; thermodynamics

Online: 6 September 2021 (13:23:23 CEST)

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Preprint REVIEW | doi:10.20944/preprints202206.0054.v1

Impacts of COVID-19 on Accessibility of Sexual and Reproductive Health Services: Scoping Review

Josphat Nkole, Muyembe Chisotwa, Rachael Chikumbi, Francis Bota, Mainga Mulemwa, Margareta Kasonde, Chofwe Musele, Nkisu Kasapatu, Brian Chanda Chiluba

Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: family planning service and COVID-19; maternal; Neonatal and child health service and COVID-19; sexual behaviour and COVID-19; SARSCOVID-2 and family planning

Online: 6 June 2022 (03:39:05 CEST)

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Introduction: Since its discovery in late 2019, the novel coronavirus (SARSCOVID-2) that causes COVID-19 has spread fast, prompting the World Health Organization (WHO) to designate the disease a worldwide pandemic on March 11, 2020.The epidemic has profoundly altered the preexisting global sexual and reproductive health landscape .The virus’s load has put ordinary services in jeopardy and harmed other health priorities. This encompasses both the provision and the supply of contraceptives, sexual health, new born and maternal health services. This Scoping review therefore mapped the availability evidence on the impact and effects of the COVID-19 disease outbreak on sexual and reproductive health. Methods: The methodological framework by Arksey and O’Malley guided this scoping review. A literature search was conducted from the following databases: Embase, PubMed, CINAHL, Scopus, WOS, and AJOL. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) flow diagram and the preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews (PRISMA-ScR) checklist were used to document the review process. The Strobe critical review checklist was used to determine the quality of the included studies. Results:19 studies were reviewed, out of which 4 were cross sectional studies, 1 was an observational study, 1 was a descriptive analytical study and the rest were qualitative studies .Majority of the studies showed evidence on the impact of COVID-19 and family planning service, maternal and child services, and three studies reported on COVID-19 and sexual behaviour. Five of the nineteen included studies reported on the impact of COVID-19 and family planning service. Conclusion: This scoping review has granted the assessment of the impact of novel SARS-CoV-2 on Sexual and reproductive health services with regards to sexual behaviour, family planning and maternal, neonatal and child health. From the 18 articles identified and reviewed, the overall responses stipulated a significant reduction in client’s utilization of services due to challenges experiences in service implementation such as stock outs. In addition, low demand for reproductive health services by clients due to restrictions imposed on the movements of people to curb the spread of the virus. It is therefore important that Governments and relevant stakeholders in Maternal and Sexual Reproductive Health prioritize development of policies and practices that protect women from the impacts of the pandemic. Furthermore, regular audits to detect trends in MSRH are necessary to inform on going mitigation efforts.

Working Paper ARTICLE

Within the Lack of Chest COVID-19 X-ray Dataset: A Novel Detection Model Based on GAN and Deep Transfer Learning

Mohamed Loey, Florentin Smarandache, Nour Eldeen M. Khalifa

Subject: Computer Science And Mathematics, Artificial Intelligence And Machine Learning Keywords: 2019 novel coronavirus; COVID-19; SARS-CoV-2; Deep Transfer Learning; Convolutional Neural Network; Machine Learning; GAN

Online: 7 April 2020 (10:59:04 CEST)

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The coronavirus (covid-19) pandemic is putting healthcare systems across the world under unprecedented and increasing pressure according to the World Health Organization (WHO). With the advances in computer algorithms and especially Artificial Intelligence, the detection of this type of virus in the early stages will help in fast recovery and help in releasing the pressure off healthcare systems. In this paper, a GAN with deep transfer learning for coronavirus detection in chest x-ray images is presented. The lack of benchmark datasets for covid-19 especially in chest x-rays images is the main motivation of this research. The main idea is to collect all the possible images for covid-19 that exists until the writing of this research and use the GAN network to generate more images to help in the detection of the virus from the available x-rays images with the highest accuracy possible. The dataset used in this research was collected from different sources and it is available for researchers to download and use it. The number of images in the collected dataset is 307 images for four different types of classes. The classes are the covid-19, normal, pneumonia bacterial, and pneumonia virus. The dataset is divided into 90% for the GAN and the training and the validation phase, while 10% used in the testing phase. The GAN helps in generating more images from the original dataset to be 30 times larger than the originally collected dataset. The GAN also help in overcoming the overfitting problem and made the proposed model more robust. Three deep transfer models are selected in this research for investigation. The models are the Alexnet, Googlenet, and Restnet18. Those models are selected based on their small number of layers on their architectures, which will reflect in reducing the complexity of the models and the consumed memory and time. Using a combination of GAN and deep transfer models prove it is efficiency according to validation, testing accuracy, and performance measurements such as precision, recall, and F1 score. Three case scenarios are tested through the paper, the first scenario which includes 4 classes from the dataset, while the second scenario includes 3 classes and the third scenario includes 2 classes. All the scenarios include the covid-19 class as it is the main target of this research to be detected. In the first scenario, the Googlenet is selected to be the main deep transfer model as it achieves 80.6% in testing accuracy. In the second scenario, the Alexnet is selected to be the main deep transfer model as it achieves 85.2% in testing accuracy, while in the third scenario which includes 2 classes(covid-19, and normal), Googlenet is selected to be the main deep transfer model as it achieves 100% in testing accuracy and 99.9% in the validation accuracy. All the performance measurement strengthen the obtained results through the research. Finally, this research may be considered one of the first trails to use GAN and deep transfer models together to help in detecting coronaviruses (covid-19) within the absence of a benchmark dataset around the world, especially in x-rays chest images.

Preprint ARTICLE | doi:10.20944/preprints202005.0332.v2

Witnessing Evolution of SARS-CoV-2 through Comparative Phylogenomics: The Proximate Origin is Guangdong, not Wuhan

Özgül Doğan, Ertan Mahir Korkmaz, Mahir Budak, Battal Çıplak, Hasan Hüseyin Başıbüyük

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: coronavirus; substitution rate; positive selection; demographic dynamics

Online: 21 June 2020 (16:10:26 CEST)

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A new form of coronavirus called severe acute respiratory disease coronavirus type 2 (SARS-CoV-2) is currently causing a pandemic. A six-month evolutionary history of SARS-CoV-2 is witnessed by characterising the total genome of 821 samples using comparative phylogenomic approaches. Our analyses produced striking inclusive results that may guide scientists/professionals for the past/future of pandemic. Phylogenetic and time estimation analyses suggest the proximate origin of pandemic strain as Guangdong and the origin time as first half of September 2019, not Wuhan and December 2019, respectively. The viral genome experienced a substitution rate similar to other RNA viruses, but it is particularly high in some of the peptides encoding sequences such as leader protein, E gene, orf8, orf10, nsp10, N gene, S gene and M gene and nsp4, while low in nsp11, orf7a, 3C-like proteinase, nsp9, nsp8 and endoRNase. Most strikingly, the divergence rate of amino acid sequences is high proportional to nucleotide divergence. Additionally, specific non-synonymous mutations in nsp3 and nsp6 evolved under positive selection. The exponential growth rate (r), doubling time (Td) and R₀ were estimated to be 47.43 per year, 5.39 days and 2.72, respectively. Comparison of synapomorphies distinguishing the SARS-CoV-2 and the candidate ancestor bat coronavirus indicates that mutation pattern in nsp3 and S gene enabled the new strain to invade human and become a pandemic strain. We arrive at the following main conclusions: (i) six months evolution of viral genome is nearly neutral, (ii) origin of pandemic is not Wuhan and predates formal reports, (iii) although viral population is ongoing an exponential growth, the doubling time is evolving towards shortening, and (iv) divergence rate of total genome is similar to other RNA viruses, but it is prominently high in some genes while low in some others and evolution in these genes should be closely monitored as their protein products intervening to pathogenicity, virulence and immune response.

Preprint ARTICLE | doi:10.20944/preprints202103.0647.v1

First Description of Natural SARS-CoV-2 Infection in Two Wild American Minks (Neovison vison)

Jordi Aguiló-Gisbert, Miguel Padilla-Blanco, Victor Lizana, Elisa Maiques, Marta Muñoz Baquero, Eva Chillida-Martínez, Jesús Cardells, Consuelo Rubio-Guerri

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: American Mink; COVID-19; Neovison vison; SARS-CoV-2; Spike; wildlife

Online: 25 March 2021 (16:39:13 CET)

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Preprint REVIEW | doi:10.20944/preprints202006.0321.v1

Hesperidin and SARS-CoV-2: New Light on the Healthy Functions of Citrus Fruit

Paolo Bellavite, Alberto Donzelli

Subject: Biology And Life Sciences, Food Science And Technology Keywords: Citrus fruits; Citrus sinensis; hesperidin; COVID-19; vitamin C; SARS-CoV-2; sweet orange

Online: 28 June 2020 (08:45:24 CEST)

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Preprint BRIEF REPORT | doi:10.20944/preprints202004.0004.v1

Transmission Potential and Severity of COVID-19 in Pakistan

Sohail Raza

Subject: Biology And Life Sciences, Virology Keywords: COVID-19, Pakistan, Economic Losses, Disease Spread, SARS-CoV-2

Online: 1 April 2020 (09:19:30 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202004.0003.v2

Computational Screening for Potential Drug Candidates Against SARS-CoV-2 Main Protease

Bruno Andrade, Preetam Ghosh, Debmalya Barh, Sandeep Tiwari, Raner José Santana Silva, Wagner Rodrigues de Assis Soares, Tarcisio Silva Melo, Andria dos Santos Freitas, Patrícia González-Grande, Lucas Sousa Palmeira, Luiz Carlos Junior Alcantara, Marta Giovanetti, Aristóteles Góes-Neto, Vasco Ariston de Carvalho Azevedo

Subject: Biology And Life Sciences, Virology Keywords: SARS-CoV-2; protease; virtual screening; pharmacophore; inhibitors; natural compounds

Online: 17 April 2020 (11:00:55 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202005.0195.v1

Single-Cell RNA-seq Identifies Cell Subsets in Human Placenta That Highly Expresses Factors to Drive Pathogenesis of SARS-CoV-2

Nancy Ashray, Anshul Bhide, Priyanka Chakarborty, Stacy Colaco, Anuradha Mishra, Karisma Chhabria, Mohit Kumar Jolly, Deepak Modi

Subject: Biology And Life Sciences, Cell And Developmental Biology Keywords: Placenta; trophoblast; SARS-CoV-2; Coronaviruses; COVID-19; Single cell RNAseq; scRNA-seq; ACE2; TMPRSS2; CD147; CTSL; inflammation

Online: 11 May 2020 (12:50:48 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202010.0114.v1

Role of Cigarette Smoke on ACE-2 Protein Membrane Expression in Bronchial Epithelial Cells Using an Air-Liquid Interface Model

Massimo Caruso, Alfio Distefano, Rosalia Emma, Michelino Di Rosa, Giuseppe Carota, Sonja Rust, Riccardo Polosa, Pietro Zuccarello, Margherita Ferrante, Giuseppina Raciti, Giovanni Li Volti

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: ACE-2; nicotine; smoke; cigarette; epithelial cells.

Online: 6 October 2020 (09:43:40 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202005.0407.v1

The SARS-CoV-2 Spike Protein D614G Mutation Shows Increasing Dominance and May Confer a Structural Advantage to the Furin Cleavage Domain

Leyan Tang, Allison Schulkins, Chun-Nan Chen, Kurt Deshayes, John S. Kenney

Subject: Biology And Life Sciences, Virology Keywords: SARS-CoV-2; spike protein; D614G mutation; genotype distribution; furin cleavage site; secondary structure; sequence analysis; homology modeling

Online: 24 May 2020 (20:31:16 CEST)

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Preprint COMMUNICATION | doi:10.20944/preprints202004.0304.v1

Neurological Complications of Pandemic COVID-19: What Have We Got So Far?

Isabelle Pastor Bandeira, Marco Antônio Machado Schlindwein, Leticia Caroline Breis, Jean Pierre Schatzmann Peron, Marcus Vinicius Magno Gonçalves

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: COVID-19; SARS-CoV-2; Neurology; coronavirus

Online: 17 April 2020 (15:27:14 CEST)

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Preprint REVIEW | doi:10.20944/preprints202005.0141.v1

Risk of Human-to-Wildlife Transmission of SARS-CoV-2

Sophie Gryseels, Luc De Bruyn, Ralf Gyselings, Sébastien Calvignac-Spencer, Fabian Leendertz, Herwig Leirs

Subject: Biology And Life Sciences, Animal Science, Veterinary Science And Zoology Keywords: mammals; wildlife; SARS-CoV-2; human-to-wildlife transmission; COVID-19

Online: 8 May 2020 (09:56:01 CEST)

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It has been a long time since the world has experienced a pandemic with such a rapid devastating impact as the current COVID-19 pandemic. The causative agent, the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) is further unusual in that it appears capable of infecting many different mammal species. As a significant proportion of people worldwide are infected with SARS-CoV-2 and may spread the infection unknowingly before symptoms occur or without any symptoms ever occurring, there is a non-negligible risk of humans spreading SARS-CoV-2 to wildlife, in particular mammals. Because of SARS-CoV-2’s evolutionary origins in bats and reports of humans transmitting the virus to pets and zoo animals, regulations for prevention of human-to-animal transmission have so far focused mostly on these animal groups. Here, we summarize recent studies and reports that show that a wide range of distantly related mammals are likely susceptible to SARS-CoV-2 and that susceptibility or resistance to the virus is in general not predictable, or only to some extent, by phylogenetic proximity to known susceptible or resistant hosts. In the absence of solid evidence on the SARS-CoV-2 susceptibility/resistance for each of the >5,500 mammal species, we argue that sanitary precautions should be taken when interacting with any mammal species in the wild. Preventing human-to-wildlife SARS-CoV-2 transmission is important for protecting these (sometimes endangered) animals from disease, but also to avoid establishment of novel SARS-CoV-2 reservoirs in wild animals. The risk of repeated re-infection of humans from such a wildlife reservoir could severely hamper SARS-CoV-2 control efforts. For wildlife fieldworkers interacting directly or indirectly with mammals, we recommend sanitary precautions such as physical distancing, wearing face masks and gloves, and frequent decontamination, which are very similar to regulations currently imposed to prevent transmission among humans.

Preprint ARTICLE | doi:10.20944/preprints202204.0091.v1

Evidence-Based Evaluation of PCR Diagnostics for SARS-Cov-2 and The Omicron Variants by Sanger Sequencing

Sin Hang Lee

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: SARS-CoV-2; SARS-CoV; RT-PCR; Sanger sequencing; RT-qPCR; receptor-binding domain (RBD); N-terminal domain (NTD); Omicron; multi-allelic SNPs; false-positive

Online: 12 April 2022 (03:57:29 CEST)

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Working Paper ARTICLE

A Preceding Low-virulence Strain Pandemic Inducing Immunity Against COVID-19

Hagai Perets, Ruth Perets

Subject: Biology And Life Sciences, Virology Keywords: COVID-19; low-virulence; high-virulence; pandemic; T-cell; immunity; virus; SARS-CoV-2

Online: 16 July 2020 (13:02:40 CEST)

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Abstract The COVID-19 pandemic is thought to began in Wuhan, China in December 2019. Mobility analysis identified East-Asia and Oceania countries to be highly-exposed to COVID-19 spread, consistent with the earliest spread occurring in these regions. However, here we show that while a strong positive correlation between case-numbers and exposure level could be seen early-on as expected, at later times the infection-level is found to be negatively correlated with exposure-level. Moreover, the infection level is positively correlated with the population size, which is puzzling since it has not reached the level necessary for population-size to affect infection-level through herd immunity. These issues are resolved if a low-virulence Corona-strain (LVS) began spreading earlier in China outside of Wuhan, and later globally, providing immunity from the later appearing high-virulence strain (HVS). Following its spread into Wuhan, cumulative mutations gave rise to the emergence of an HVS, known as SARS-CoV-2, starting the COVID-19 pandemic. We model the co-infection by an LVS and an HVS, and show that it can explain the evolution of the COVID-19 pandemic and the non-trivial dependence on the exposure level to China and the population-size in each country. We find that the LVS began its spread a few months before the onset of the HVS, and that its spread doubling-time is

\sim 1.59 \pm 0.17

times slower than the HVS. Although more slowly spreading, its earlier onset allowed the LVS to spread globally before the emergence of the HVS. In particular, in countries exposed earlier to the LVS and/or having smaller population-size, the LVS could achieve herd-immunity earlier, and quench the later-spread HVS at earlier stages. We find our two-parameter (the spread-rate and the initial onset time of the LVS) can accurately explain the current infection levels (R^2

=0.74

; correlation p-value (p) of 5x10^-13

). Furthermore, countries exposed early should have already achieved herd-immunity. We predict that in those countries cumulative infection levels could rise by no more than 2-3 times the current level through local-outbreaks, even in the absence of any containment measures. We suggest several tests and predictions to further verify the double-strain co-infection model and discuss the implications of identifying the LVS.

Preprint REVIEW | doi:10.20944/preprints202104.0481.v1

Minimizing Errors in RT-PCR Detection and Quantification of SARS-CoV-2 RNA for Wastewater Surveillance

Warish Ahmed, Stuart Simpson, Paul Bertsch, Kyle Bibby, Aaron Bivins, Linda Blackall, Silvia Bofill-Mas, Albert Bosch, Joao Brandao, Phil Choi, Mark Ciesielski, Erica Donner, Nishita D'Souza, Andreas Farnleitner, Daniel Gerrity, Raul Gonzalez, John Griffith, Pradip Gyawali, Charles Haas, Kerry Hamilton, Chanditha Hapuarachchi, Valerie Harwood, Rehnuma Haque, Greg Jackson, Stuart Khan, Wesaal Khan, Masaaki Kitajima, Asja Korajkic, Giuseppina La Rosa, Blythe Layton, Erin Lipp, Sandra McLellan, Brian McMinn, Gertjan Medema, Suzanne Metcalfe, Wim Meijer, Jochen Mueller, Heather Murphy, Colleen Naughton, Rachel Noble, Sudhi Payyappat, Susan Petterson, Tarja Pitkanen, Veronica Rajal, Brandon Reyneke, Fernando Roman, Joan Rose, Marta Rusinol, Michael Sadowsky, Laura Sala-Comorera, Yin Xiang Setoh, Samendra Sherchan, Kwanrawee Sirikanchana, Wendy Smith, Joshua Steele, Rosalie Sabburg, Erin Symonds, Phong Thai, Kevin Thomas, Josh Tynan, Simon Toze, Janelle Thompson, Andy Whiteley, Judith Wong, Daisuke Sano, Stefan Wuertz, Irene Xagoraraki, Qian Zhang, Amity Zimmer-Faust, Orin Shanks

Subject: Environmental And Earth Sciences, Waste Management And Disposal Keywords: COVID-19; SARS-CoV-2; Wastewater; Surveillance; False-positive; False-negative; RT-PCR

Online: 19 April 2021 (13:08:13 CEST)

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Wastewater surveillance for pathogens using the reverse transcription-polymerase chain reaction (RT-PCR) is an effective, resource-efficient tool for gathering additional community-level public health information, including the incidence and/or prevalence and trends of coronavirus disease-19 (COVID-19). Surveillance of SARS-CoV-2 in wastewater may provide an early-warning signal of COVID-19 infections in a community. The capacity of the world’s environmental microbiology and virology laboratories for SARS-CoV-2 RNA characterization in wastewater is rapidly increasing. However, there are no standardized protocols nor harmonized quality assurance and quality control (QA/QC) procedures for SARS-CoV-2 wastewater surveillance. This paper is a technical review of factors that can lead to false-positive and -negative errors in the surveillance of SARS-CoV-2, culminating in recommendations and strategies that can be implemented to identify and mitigate these errors. Recommendations include, stringent QA/QC measures, representative sampling approaches, effective virus concentration and efficient RNA extraction, amplification inhibition assessment, inclusion of sample processing controls, and considerations for RT-PCR assay selection and data interpretation. Clear data interpretation guidelines (e.g., determination of positive and negative samples) are critical, particularly during a low incidence of SARS-CoV-2 in wastewater. Corrective and confirmatory actions must be in place for inconclusive and/or potentially significant results (e.g., initial onset or reemergence of COVID-19 in a community). It will also be prudent to perform inter-laboratory comparisons to ensure results are reliable and interpretable for ongoing and retrospective analyses. The strategies that are recommended in this review aim to improve SARS-CoV-2 characterization for wastewater surveillance applications. A silver lining of the COVID-19 pandemic is that the efficacy of wastewater surveillance was demonstrated during this global crisis. In the future, wastewater will play an important role in the surveillance of a range of other communicable diseases.

Preprint ARTICLE | doi:10.20944/preprints202004.0311.v1

COVID-19 Outbreak Prediction with Machine Learning

Sina F. Ardabili, Amir Mosavi, Pedram Ghamisi, Filip Ferdinand, Annamaria R. Varkonyi-Koczy, Uwe Reuter, Timon Rabczuk, Peter M. Atkinson

Subject: Computer Science And Mathematics, Artificial Intelligence And Machine Learning Keywords: COVID-19; coronavirus disease; coronavirus; SARS-CoV-2; model; prediction; machine learning

Online: 19 April 2020 (01:47:10 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202003.0242.v1

A Putative Prophylactic Solution for COVID-19: Development of Novel Multiepitope Vaccine Candidate against SARS‐COV‐2 by Comprehensive Immunoinformatic and Molecular Modelling Approach

Hafiz Muzzammel Rehman, Muhammad Usman Mirza, Mahjabeen Saleem, Matheus Froeyen, Sarfraz Ahmad, Roquyya Gul, Muhammad Shahbaz Aslam, Muhammad Sajjad, Munir Ahmad Bhinder

Subject: Biology And Life Sciences, Virology Keywords: COVID-19; SARS-CoV-2; spike protein; multiepitope vaccine; molecular modeling

Online: 15 March 2020 (12:45:54 CET)

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Preprint HYPOTHESIS | doi:10.20944/preprints202005.0359.v1

Entry of SARS-CoV2 through the Basal Surface of Alveolar Endothelial Cells – A Proposed Mechanism Mediated by CD147 in COVID-19

Francia Acosta Saltos, Alejandro David Acosta Saltos

Subject: Biology And Life Sciences, Virology Keywords: Covid-19; Endothelial; CD147; SARS-CoV2

Online: 23 May 2020 (05:26:13 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202002.0230.v1

Evaluating the Traditional Chinese Medicine (TCM) Officially Recommended in China for COVID-19 Using Ontology-Based Side-Effect Prediction Framework (OSPF) and Deep Learning

Zeheng Wang, Liang Li, Jing Yan, Yuanzhe Yao

Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: side effect; tranditional Chinese medicine; COVID-19; artificial intelligence; coronavirus

Online: 17 February 2020 (01:18:13 CET)

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Ethnopharmacological relevance: Novel coronavirus disease (COVID-19) outbroke in Wuhan has imposed a huge influence onto the society in term of the public heath and economy. However, so far, no effective drugs or vaccines have been developed. Whereas, the Traditional Chinese Medicine (TCM) has been considered as a promising supplementary treatment for the disease owing to its clinically proven performance on many diseases even like severe acute respiratory syndrome (SARS). Meanwhile, many side-effect (SE) reports suggest the SE of the TCM prescriptions cannot be ignored in curing the COVID-19, especially because COVID-19 always simultaneously leads to dramatic degradation of the patients’ physical condition. How to evaluate the TCM regarding to their latent SE is a urgent challenge. Aim of the study: In this study, we use an ontology-based side-effect prediction framework (OSPF) developed in our previous work and Artificial Neural Network (ANN)-based deep learning to evaluate the TCM prescriptions that are officially recommended in China for novel coronavirus (COVID-19). Materials and methods: Firstly, we adopted the OSPF developed in our previous work, where an ontology-based model separate all the ingredients in a TCM prescription into two categories: hot and cold. Then, we established a database by converting each TCM prescription into a vector containing the ingredient dosage and the according hot/cold attribution as well as the safe/unsafe label. And, we trained the ANN model using this database, after which a safety indicator (SI), as the complementary percentage of side-effect (SE) possibility, is then given for each TCM prescription. According to the proposed SI from high to low, we re-organize the recommended prescription list. Secondly, by using this method, we also evaluate the safety indicators of some other famous TCM prescriptions that are not in the recommended list but are used traditionally to cure flu-like diseases for extending the potential treatments. Results: Based on the SI generated in the ANN model, FTS, PMSP, and SF are the safest ones in recommended list, which all own a more-than-0.8 SI. Whereas, JHQG, LHQW, SFJD, XBJ, and SHL are the prescriptions that are most likely unsafe, where the indicators are all below 0.2. In the extra list, the indicators of XC, XQRS, CC, and CHBX are all above 0.8, and at the meantime, XZXS, SJ, QW, and KBD’s indicators are all below 0.2. Conclusions: In total, there are seven TCM prescriptions which own the indicators more than 0.8, suggesting these prescriptions should be considered firstly in curing COVID-19, if suitable. We believe this work will provide a reasonable suggestion for the society to choose proper TCM as the supplementary treatment for COVID-19. Besides, this work also introduces a pilot and enlightening method for creating a more reasonable recommendation list of TCM to other diseases.

Preprint ARTICLE | doi:10.20944/preprints202003.0372.v1

Inhibitors of SARS-CoV-2 Main Protease from a Library of Marine Natural Products: A Virtual Screening and Molecular Modeling Study

Davide Gentile, Vincenzo Patamia, Angela Scala, Maria Teresa Sciortino, Anna Piperno, Antonio Rescifina

Subject: Chemistry And Materials Science, Medicinal Chemistry Keywords: COVID-19; SARS-CoV-2; Marine natural product; Virtual screening; Docking

Online: 25 March 2020 (08:23:57 CET)

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Preprint ARTICLE | doi:10.20944/preprints202005.0442.v1

Knowledge, Awareness and Perceptions of Coronavirus Disease 2019 (COVID-19) in a Cohort of Indian Dental Professionals: A Questionnaire-Based Study

Niraj Kinariwala, Lakshman Samaranayake, Irosha Perera, Zeal Patel

Subject: Medicine And Pharmacology, Dentistry And Oral Surgery Keywords: COVID-19; knowledge; awareness; perceptions; Indian dentists; coronavirus

Online: 27 May 2020 (07:56:19 CEST)

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Preprint REVIEW | doi:10.20944/preprints202011.0558.v1

Recombinant Protein Vaccines, a Proven Approach Against Coronavirus Pandemics

Jeroen Pollet, Wen-Hsiang Chen, Ulrich Strych

Subject: Biology And Life Sciences, Virology Keywords: SARS-CoV-2; COVID-19; Adjuvants; Vaccine Production; Vaccine Delivery; Clinical Trials; Neutralizing Antibodies; Th1

Online: 22 November 2020 (11:57:51 CET)

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Preprint ARTICLE | doi:10.20944/preprints202006.0031.v3

A Fully Automated Deep Learning-based Network For Detecting COVID-19 from a New And Large Lung CT Scan Dataset

Mohammad Rahimzadeh, Abolfazl Attar, Seyed Mohammad Sakhaei

Subject: Computer Science And Mathematics, Artificial Intelligence And Machine Learning Keywords: Deep learning; Convolutional Neural Network; Coronavirus; COVID-19; radiology; CT scan; Medical image analysis; Automatic medical diagnosis; lung CT scan dataset

Online: 5 September 2020 (03:36:20 CEST)

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Preprint REVIEW | doi:10.20944/preprints202006.0216.v2

Detection and Survival of SARS-coronavirus in Human Stool, Urine, Wastewater and Sludge

Andrew Singer, Rachel Wray

Subject: Biology And Life Sciences, Virology Keywords: SARS-coronavirus; Severe Acute Respiratory Syndrome; COVID-19; Stool; Urine; Wastewater; Wastewater-based epidemiology

Online: 18 June 2020 (09:29:00 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202005.0397.v1

Genetic Uniformity of a Specific Region in SARS-CoV-2 Genome and In-Silico Target-Oriented Repurposing of N-Acetyl-D-Glucosamine

Omur Baysal, Ragip Soner Silme, Cagatay Karaaslan

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: SARS-CoV-2; Drug repurposing; N-acetyl-D-glucosamine; ORF1ab; Biodata mining; Protein modelling

Online: 24 May 2020 (18:49:41 CEST)

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Preprint REVIEW | doi:10.20944/preprints202004.0272.v1

Anosmia and Ageusia as Initial or Unique Symptoms after SARS-COV-2 Virus Infection

Calixto Machado, Joel Victor Gutierrez

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: SARS-CoV-2 (CoV-2); COVID-19; coronavirus; pandemic; smell; anosmia; taste; ageusia

Online: 16 April 2020 (12:42:44 CEST)

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Preprint REVIEW | doi:10.20944/preprints202003.0348.v1

An Update on SARS-COV-2/COVID-19 with Particular Reference on Its Clinical Pathology, Pathogenesis, Immunopathology and Mitigation Strategies – A Review

Kuldeep Dhama, Shailesh Kumar Patel, Mamta Pathak, Mohd. Iqbal Yatoo, Ruchi Tiwari, Yashpal Singh Malik, Rajendra Singh, Ranjit Sah, Ali A. Rabaan, D. Katterine Bonilla-Aldana, Alfonso J. Rodriguez-Morales

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: SARS-COV-2; COVID-19; clinical pathology; pathogenesis; immunopathology

Online: 23 March 2020 (07:51:17 CET)

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Coronavirus Disease 2019 (COVID-19), caused by a novel coronavirus named Severe Acute Respiratory Syndrome - Coronavirus-2 (SARS-CoV-2), emerged in early December 2019 in China and attained a pandemic situation worldwide by its rapid spread to nearly 167 countries with 287.239 confirmed cases and 11.921 human deaths with a case fatality rate (CFR) of around 4 per cent. Bats were considered as the reservoir host, and the search of a probable intermediate host is still going on. Animals have anticipated culprit of SARS-CoV-2 as of now. The disease is mainly manifested by pneumonia and related respiratory signs and symptoms, but the involvement of the gastrointestinal system and nervous system is also suggested. The severe form of the disease associated with death is mainly reported in older and immune-compromised patients with pre-existing disease history. Death in severe cases is attributed to respiratory failure associated with hyperinflammation. Cytokine storm syndrome associated with rampant inflammation in response to SARS-CoV-2 infection is considered as the leading killer of COVID-19 patients. COVID-19 patients were reported with higher levels of many pro-inflammatory cytokines and chemokines like IFN-g, IL-1b, IP-10, and MCP-1. Furthermore, severe cases of COVID-19 revealed higher levels of TNF-α, G-CSF, and MIP-1A. Blood profile of the COVID-19 patients exhibits lymphopenia, leucopenia, thrombocytopenia and RNAaemia along with increased levels of aspartate aminotransferase. SARS-CoV-2 infection in pregnant women does not lead to fetus mortalities unlike other zoonotic coronaviruses like SARS-CoV and MERS-CoV, with no evidence of intrauterine transmission to neonates. Rapid and confirmatory diagnostics have been developed, and high efforts are being made to develop effective vaccines and therapeutics. In the absence of any virus-specific therapeutic, internationally health care authorities are recommending adoption of effective prevention and control measures to counter and contain this pandemic virus. This paper is an overview of this virus and the disease with a particular focus on SARS-COV-2 / COVID-19 clinical pathology, pathogenesis and immunopathology along with a few recent research developments.

Preprint ARTICLE | doi:10.20944/preprints202003.0325.v1

A Retrospective Analysis of Influence of Environmental/Air Temperature and Relative Humidity on SARS-CoV-2 Outbreak

Md. Arifur Rahman, Md. Golzar Hossain, Atul Chandra Singha, Md Sayeedul Islam, Md Ariful Islam

Subject: Biology And Life Sciences, Virology Keywords: SARS-CoV-2; COVID-19; infectivity; temperature; humidity

Online: 23 March 2020 (01:30:06 CET)

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Preprint ARTICLE | doi:10.20944/preprints202007.0719.v1

Long-term Existence of SARS-CoV-2 in COVID-19 Patients: Host Immunity, Viral Virulence, and Transmissibility

Meilin Jin, Xingyu Wang, Haini Jiang, Lijuan Hua, Weiwei Yu, dan ding, ke wang, Xiaopan Li, Kun Huang, Zhong zou, Shuyun Xu

Subject: Biology And Life Sciences, Virology Keywords: SARS-CoV-2; long-term; neutralization antibody; lymphocyte functionality; viral pathogenicity.

Online: 30 July 2020 (12:16:21 CEST)

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