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Preprint ARTICLE | doi:10.20944/preprints202310.1276.v1

Genomic analysis and tracking of SARS-CoV-2 variants in Gwangju, South Korea from 2020 to 2022

Yeong-Un Lee, Kwangho Lee, Hongsu Lee, Jung wook Park, Sun-Ju Cho, Ji-Su Park, Jeongeun Mun, Sujung Park, Cheong-mi Lee, Juhye Lee, Mihee Seo, Eunju Kim, Jinjong Seo, Yonghwan Kim, Sun-Hee Kim, Yoon-Seok Chung

Subject: Biology And Life Sciences, Virology Keywords: COVID-19; SARS-CoV-2; whole-genome sequencing; variants; lineages

Online: 19 October 2023 (11:25:35 CEST)

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Preprint REVIEW | doi:10.20944/preprints202308.0196.v1

“When”, “Where”, and “How” of SARS-CoV-2 Infection Affects the Human Cardiovascular System: a Narrative Review

Nicholas G. Kounis, Christos Gogos, Cesare de Gregorio, Ming-Yow Hung, Sophia N. Kouni, Efthymios P. Tsounis, Stelios F. Assimakopoulos, Soheila Pourmasumi, Virginia Mplani, George Servos, Periklis Dousdampanis, Panagiotis Plotas, Marina A. Michalaki, Grigorios Tsigkas, Gerasimos Grammatikopoulos, Dimitrios Velissaris, Ioanna Koniari

Subject: Biology And Life Sciences, Life Sciences Keywords: ACE2 receptors; COVID-19; cardiac complications, kinin-kallikrein; Kounis syndrome

Online: 2 August 2023 (10:07:00 CEST)

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The novel severe acute respiratory coronavirus-2 (SARS-Cov-2) constitutes the causative agent of coronavirus disease-2019 (COVID-19). Several mechanisms have been proposed regarding the development of cardiovascular complications during and after acute COVID-19 infection. COVID-19, caused by SARS-CoV-2, has emerged as one of the deadliest pandemics in modern history. Several clinical and pathophysiologic mechanisms have been proposed for development of cardiovascular complications during and after acute COVID-19 infection. The myocardial injury in patients with COVID-19 has been attributed to coronary spasm, microthrombi formation, plaque rupture, hypoxic injury or cytokine storm disposing the same pathophysiology with the three clinical variants of Kounis syndrome. One of the main proposed mechanisms for development of cardiovascular complications is the angiotensin converting enzyme 2 (ACE2) and its interactions with the renin-aldosterone system (RAAS) and the kinin-kallikrein system (KKS). The ACE2 receptors are expressed throughout the human body located mainly in heart, blood vessels endothelium, lungs, intestines, testes and neurons. The SARS-CoV-2 directly invades the endothelial cells that contain ACE2 receptors and constitutes the main pathway through which the virus enters the endothelial cells. This leads to downregulation of the ACE2 receptors and causes angiotensin II accumulation leading to prothrombotic effects such as hemostatic imbalance via activation of the coagulation cascade, impaired fibrinolysis, thrombin generation, vasoconstriction, endothelial and platelet activation, and pro-inflammatory cytokine release. Indeed, angiotensin I exerts no direct biological function except that its high levels can stimulate catecholamine production. It is metabolized to its biologically active byproduct angiotensin II, a potent vasoconstrictor, by angiotensin converting enzyme (ACE) through cleavage of the two terminal amino acids. SARS-CoV-2 infection prevents the counterbalancing action of the KKS system that normally causes vasodilation and regulates tissue repair, inflammation, cell proliferation, and platelet aggregation. All this cascade leads to the following cardiovascular events: cardiac arrhythmias, cardiac arrest, cardiomyopathy, cytokine storm, heart failure, ischemic myocardial injuries and microvascular disease, Kounis syndrome, long COVID, myocardial fibrosis, myocarditis, new onset hypertension, pericarditis, postural orthostatic tachycardia syndrome (POTS), pulmonary hypertension, stroke, Takotsubo Syndrome, venous thromboembolism and thrombocytopenia. In this narrative review we describe and elucidate when and how the COVID-19 affects the human cardiovascular system, in various areas on the human body that are vulnerable in every category of patients including children and athletes.

Preprint REVIEW | doi:10.20944/preprints202305.1219.v1

Biology and Behavior of SARS-COV-2 Contagion with Emphasis on Treatment Strategies, Risk Assessment, and Resilience

James Baldwin, Samina Noorali, Ashok Vaseashta

Subject: Biology And Life Sciences, Virology Keywords: COVID-19; risk assessment; mitigation; resilience; pandemic modeling; lessons learned

Online: 17 May 2023 (09:59:40 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202304.0861.v1

Prevalence of SARS-CoV-2 Infections and the Percentage of Deaths Among Infected Healthcare Workers in Poland

Marek Wojczyk, Ewa Niewiadomska, Małgorzata Kowalska

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: COVID-19; healthcare workers; pandemics; SARS-CoV-2; vaccination coverage

Online: 24 April 2023 (13:51:21 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202301.0586.v1

Experimental Lung Inflammation Induced by Inactivated SARS-CoV-2 is Controlled by Intranasal Instillation of Vitamin D

William Danilo Fernandes de Souza, Sofia Fernanda Gonçalves Zorzella-Pezavento, Marina Caçador Ayupe, Caio Loureiro Salgado, Bernardo de Castro Oliveira, Francielly Moreira, Guilherme William da Silva, Stefanie Primon Muraro, Gabriela Fabiano de Souza, José Luiz Proença-Módena, Joao Pessoa Araujo-Junior, Denise Fonseca, Alexandrina Sartori

Subject: Biology And Life Sciences, Virology Keywords: SARS-CoV-2; COVID-19; lung; inflammation; mice; vitamin D

Online: 31 January 2023 (12:04:19 CET)

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Preprint BRIEF REPORT | doi:10.20944/preprints202208.0081.v1

Pathological Evidence for Residual SARS-CoV-2 in the Micrometastatic Niche of a Patient with Ovarian Cancer

Takuma Hayashi, Kenji Sano, Nobuo Yaegashi, Ikuo Konishi

Subject: Biology And Life Sciences, Virology Keywords: SARS-CoV-2; COVID-19; micrometastatic niche; Patient with Cancer

Online: 3 August 2022 (10:22:20 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202012.0258.v1

Prevalence of Co-Infections With Respiratory Viruses in Individuals Investigated for Sars-Cov-2 in Ontario, Canada

Adriana Peci, Vanessa Tran, Jennifer L Gurtherie, Ye Li, Paul Nelson, Kevin L Schwartz, Sara A Buchan, Jonathan B Gubbay

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: co-infection; SARS-CoV-2; Covid-19; seasonal respiratory viruses

Online: 10 December 2020 (12:53:28 CET)

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Preprint CONCEPT PAPER | doi:10.20944/preprints202004.0412.v1

Think Different with RNA Therapy: Can Antisense Oligonucleotides Be Used to Inhibit Replication and Transcription of SARS-Cov-2?

Eric Barrey, Veronica Burzio, Sophie Dhorne-Pollet, Jean-François Eléouët, Bernard Delmas

Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: coronavirus; COVID-19; antisense oligonucleotide; ASO; LNA GapmeR

Online: 23 April 2020 (11:30:39 CEST)

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The severity of the global COVID-19 pandemic, with a high transmission rate, 2.6-4.7% lethality and a huge economic impact, poses an urgent need for efficient medical treatments and vaccines. Currently, there are only non-specific treatments to assist the patients in acute respiratory distress during the inflammatory step following the preliminary infection by SARS-CoV-2. Clinical trials of drug repurposing were quickly launched at the international level. Specific treatments such as the transfusion of plasma from patients who have recovered into infected patients or the use of specific inhibitors of the viral RNA-polymerase complex are promising strategies to block infection. To complete the therapeutic arsenal, we believe that the opportunity of targeting the SARS-CoV-2 genome by RNA therapy should be deeply investigated. In the present paper, we propose to design specific antisense oligonucleotides targeting transcripts encoding viral proteins associated to replication and transcription of SARS-CoV-2, aiming to block infection. We designed antisense oligonucleotides targeting the genomic 5’ untranslated region (5’-UTR), open reading frames 1a and 1b (ORF1a and ORF1b) governing expression of the replicase/transcriptase complex, and the gene N encoding the nucleoprotein that is genome-associated. To maximize the probability of efficiency, we predicted the antisense oligonucleotides by using two design methods: i) conventional antisense oligonucleotides with 100% phosphorothioate modifications (ASO); ii) antisense locked nucleic acids GapmeR. After binding the viral RNA target, the hetero-duplexes antisense oligonucleotide-RNA are cleaved by RNAse H1. Nine potent ASO candidates were found and we selected five of them targeting ORF1a (3), ORF1b (1) and N (1). Nine GapmeR candidates were predicted with excellent properties and we retained four of them targeting 5’-UTR (1), ORF1a (3), ORF1b (1) and N (1). The most potent GapmeR candidate targets the 5’-UTR, a key genomic domain with multiple functions in the viral cycle. By this open publication, we are pleased to share these in silico results with the scientific community in hopes of stimulating innovation in translational research in order to fight the unprecedented COVID-19 pandemic. These antisense oligonucleotide candidates should be now experimentally evaluated.

Preprint ARTICLE | doi:10.20944/preprints202308.0387.v1

Acquisition of Humoral Immune Responses in Convalescent Japanese People with SARS-CoV-2 (COVID-19) Infection in 2021

Koshiro Monzen, Takanori Watanabe, Toshihiro Okabe, Hisakuni Sekino, Hironori Nakagami, Ryuichi Morishita

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: COVID-19; SARS-CoV-2; Convalescent serum; Neutralizing antibody

Online: 4 August 2023 (12:35:21 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202205.0319.v1

ORFeome Phage Display Reveals a Major Immunogenic Epitope on the S2 Subdomain of SARS-Cov-2 Spike Protein

Rico Ballmann, Sven-Kevin Hotop, Federico Bertoglio, Stephan Steinke, Philip Alexander Heine, M.-Zeeshan Chaudhry, Dieter Jahn, Boas Pucker, Fausto Baldanti, Antonio Piralla, Maren Schubert, Luka Čičin-Šain, Michael Hust, Stefan Dübel

Subject: Biology And Life Sciences, Virology Keywords: phage display; epitope mapping; COVID-19; genomic library; NGS

Online: 24 May 2022 (04:20:15 CEST)

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Preprint REVIEW | doi:10.20944/preprints202006.0319.v1

SARS-CoV-2 Impact on the Central Nervous System: Are Astrocytes and Microglia Main Players or Merely Bystanders?

Veronica Murta, Alejandro Villarreal, Alberto Javier Ramos

Subject: Biology And Life Sciences, Virology Keywords: glia; central nervous system; COVID-19; SARS; MERS; coronavirus

Online: 26 June 2020 (17:32:55 CEST)

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With confirmed COVID-19 cases surpassing the 8.5 million mark around the globe, there is an imperative need to deepen the efforts from the international scientific community to gain comprehensive understanding of SARS-CoV-2. Although the main clinical manifestations are associated with respiratory or intestinal symptoms, reports of specific and non-specific neurological signs and symptoms, both at presentation or during the course of the acute phase, are increasing. Approximately 25-40% of the patients present neurological symptoms. The etiology of these neurological manifestations remains obscure, and probably involves several direct pathways, not excluding the direct entry of the virus to the Central Nervous System (CNS) through the olfactory epithelium, circumventricular organs, or disrupted blood-brain barrier (BBB). Furthermore, neuroinflammation might occur in response to the strong systemic cytokine storm described for COVID-19, or due to dysregulation of the CNS angiotensin system. Descriptions of neurological manifestations in patients in the previous coronavirus (CoV) outbreaks have been numerous for the SARS-CoV and lesser for MERS-CoV. Strong evidence from patients and experimental models suggests that some human variants of CoV have the ability to reach the CNS and that neurons, astrocytes and/or microglia can be target cells for CoV. A growing body of evidence shows that astrocytes and microglia have a major role in neuroinflammation, responding to local CNS inflammation and/or to dysbalanced peripheral inflammation. This is another potential mechanism for SARS-CoV-2 damage to the CNS. In this work we will summarize the known neurological manifestations of SARS-CoV-2, SARS-CoV and MERS-CoV, explore the potential role for astrocytes and microglia in the infection and neuroinflammation, and compare them with the previously described human and animal CoV that showed neurotropism. We also propose possible underlying mechanisms by focusing on our knowledge of glia, neurons, and their dynamic intricate communication with the immune system.

Preprint CASE REPORT | doi:10.20944/preprints202004.0446.v1

Central Disequilibrium Could be an Early Sign and Symptom of Rapidly Progressive SARS-CoV-2 related Respiratory Failure

Ali Zreik, Ali Ammar, Charles. Hunley, Mario Madruga, Rumi Khan

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Central Disequilibrium; CNS; covid-19 coronavirus; SARS-CoV-2

Online: 24 April 2020 (14:07:43 CEST)

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Preprint HYPOTHESIS | doi:10.20944/preprints202004.0090.v1

Hydroxychloroquine as an Aerosol Might Markedly Reduce and Even Prevent Severe Clinical Symptoms after SARS-CoV-2 Infection

Ansgar Klimke, Gudrun Hefner, Bianca Will, Ursula Voss

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: COVID-19: hydroxychloroquine aerosol; pharmacotherapy; prevention; SARS-CoV-2

Online: 7 April 2020 (11:11:09 CEST)

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

Preprint ARTICLE | doi:10.20944/preprints202103.0258.v1

Potent Antiviral Activity Against HSV-1 and SARS-CoV-2 by Antimicrobial Peptoids

Gill Diamond, Natalia Molchanova, Claudine Herlan, John A. Fortkort, Jennifer S. Lin, Erika Figgins, Nathan Bopp, Lisa K. Ryan, Donghoon Chung, Robert Scott Adcock, Michael Sherman, Annelise E. Barron

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Antivirals; peptoids; LL-37; air-liquid interface; cytotoxicity; membrane disruption; COVID-19; HSV-1; SARS-CoV-2

Online: 9 March 2021 (10:25:03 CET)

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Preprint REVIEW | doi:10.20944/preprints202009.0526.v1

Nucleic Acid and Immunological Diagnostics for SARS-CoV-2: Processes, Platforms and Pitfalls

Avinash Premraj, Abi George Aleyas, Binita Nautiyal, Thaha Jamal Rasool

Subject: Biology And Life Sciences, Virology Keywords: COVID-19 testing; molecular diagnostics; immunological testing; RT-qPCR; ELISA; pool PCR; lateral flow assay; rapid assay

Online: 23 September 2020 (03:33:12 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202403.1260.v1

Humoral immunity across the SARS-CoV-2 Spike after Sputnik V (Gam‑COVID‑Vac) vaccination

Alejandro Cornejo, Christopher Franco, Mariajose Rodriguez, Alexis García, Inirida Belisario, Soriuska Mayoría, Domingo Jose Garzaro, Jose Luis Zambrano, Rossana Celeste Jaspe, Mariana Hidalgo, Nereida Parra-Gimenez, Franklin Ennodio Claro, Ferdinando Liprandi, Jacobus Henri de Waard, Hector Rafael Rangel, Flor Helene Pujol

Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: COVID-19; SARS-CoV-2; Antibody; ELISA; Spike; S1; S2; RBD; epitopes; Neutralization

Online: 21 March 2024 (09:12:29 CET)

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Preprint REVIEW | doi:10.20944/preprints202308.1547.v1

Unravelling Insights into the Evolution and Management of SARS-CoV-2: A Comprehensive Review

Aganze Mushebenge, Samuel C. Ugbaja, Nonkululeko Avril Mbatha, Rene M. Khan, Hezekiel M. Kumalo

Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: Main Protease Inhibitors; SARS-CoV-2; COVID-19; mutations; vaccines; therapeutics; drug repurposing; management strategies

Online: 22 August 2023 (09:31:05 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202012.0281.v1

A COVID-19 Drug Repurposing Strategy Through Quantitative Homological Similarities by using a Topological Data Analysis Based Formalism

Raul Pérez-Moraga, Jaume Forés-Martos, Beatriz Suay, Jean-Louis Duval, Antonio Falcó, Joan Climent

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: covid-19; drug repurposing; topological data analysis; persistent homology

Online: 11 December 2020 (12:57:28 CET)

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Preprint REVIEW | doi:10.20944/preprints202008.0320.v1

Data Science in Unveiling COVID-19 Pathogenesis and Diagnosis: Evolutionary Origin to Drug Repurposing

Jayanta Kumar Das, Giuseppe Tradigo, Pierangelo Veltri, Pietro H Guzzi, Swarup Roy

Subject: Computer Science And Mathematics, Artificial Intelligence And Machine Learning Keywords: Data Science; Machine Learning; Deep Learning; Genomics; COVID-19; Drug Discovery; Image Analysis; Interactomics; Epidemiology

Online: 14 August 2020 (11:01:56 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202209.0297.v1

Effectiveness and Tolerability of Early Treatment with Monoclonal Antibodies against SARS-Cov-2: Results from A Real-Life Study before Omicron Surge

Riccardo Scotto, Antonio Riccardo Buonomo, Giulia Zumbo, Antonio Di Fusco, Nunzia Esposito, Isabella Di Filippo, Mariano Nobile, Biagio Pinchera, Nicola Schiano Moriello, Riccardo Villari, Ivan Gentile

Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: Mabs; VoC; COVID-19; real-life

Online: 20 September 2022 (07:15:52 CEST)

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Preprint REVIEW | doi:10.20944/preprints202304.0767.v1

Functional Foods: A Promising Strategy for Restoring Gut Microbiota Diversity Impacted by SARS-CoV-2 Variants

Antara Banerjee, Indumathi Somasundaram, Diptimayee Das, Samatha Jain M, Husaina Banu, Pavane MS, Sujay Paul, Atil Bisgin, Hong Zhang, Xiao-Feng Sun, Asim K Duttaroy, Surajit Pathak

Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: COVID-19; SARS-CoV-2; Gut microbiota; Variants; Probiotics; gut microbiota metabolites

Online: 23 April 2023 (04:34:31 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202209.0390.v1

Determination of SARS-CoV-2 Variants and Seroprevalence in Accra, Ghana during the Delta-Omicron Waves

Irene Owusu Donkor, Elvis Suatey Lomotey, Jewelna Akorli, Millicent Opoku, Emmanuel Frimpong Gyekye, Kojo M. Sedzro, Nana Efua Andoh, Yvonne Ashong, Benjamin Abuaku, Kwadwo Ansah Koram, Vincent Munster

Subject: Biology And Life Sciences, Virology Keywords: SARS-CoV-2; COVID-19; asymptomatic; seroprevalence; Delta variant; Omicron variant; vaccination

Online: 26 September 2022 (09:41:01 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 COMMUNICATION

Open Questions for Harnessing Autophagy-Modulating Drugs in the SARS-CoV-2 War: Hope or Hype?

Patrick Brest, Jonathan Benzaquen, Daniel J. Klionsky, Paul Hofman, Baharia Mograbi

Subject: Biology And Life Sciences, Virology Keywords: anti-viral; COVID-19; SARS-CoV-2; autophagy; chloroquine; hydroxychloroquine; immunology; infection; inflammation; lysophagy; microbiology; Plaquenil; SARS; virophagy

Online: 23 May 2020 (10:45:40 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202207.0380.v1

Molecular Mimicry between SARS-CoV-2 and Human Endocrinocytes: A Prerequisite of Post-COVID Endocrine Autoimmunity

Leonid P. Churilov, Muslimbek G. Normatov, Vladimir J. Utekhin

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: SARS-CoV-2; COVID-19; autoantibodies; autoimmune endocrinopathies; long-COVID syndrome; molecular mimicry; thyroid gland; adrenals; pituitary; Langerhans’ islets

Online: 26 July 2022 (03:42:01 CEST)

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Preprint HYPOTHESIS | doi:10.20944/preprints202004.0143.v1

Inflamm-Aging: Why Older Men Are the Most Susceptible to SARS-Cov-2 Complicated Outcomes

Massimiliano Bonafè, Francesco Prattichizzo, Angelica Giuliani, Gianluca Storci, Jacopo Sabbatinelli, Fabiola Olivieri

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: SARS-CoV-2; COVID-19; IL-6; inflamm-aging; immune senescence; host-directed therapies

Online: 9 April 2020 (08:38:22 CEST)

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Preprint REVIEW | doi:10.20944/preprints202306.0647.v1

Nanomaterials Used in the Preparation of Personal Protective Equipment (PPE) in the Fight against SARS-CoV-2

Pierantonio De Luca, Anastasia Macario, Janos B.Nagy

Subject: Chemistry And Materials Science, Nanotechnology Keywords: Covid-19; Coronaviruses; Personal protective equipment; Nanomaterials; PPE; SARS-CoV-2

Online: 8 June 2023 (13:19:25 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202007.0558.v2

Small Molecule Stabilization of Non-native Protein-Protein Interactions of SARS-CoV-2 N Protein as a Mechanism of Action against COVID-19

Martin Lavecchia, Julian Fernandez

Subject: Chemistry And Materials Science, Medicinal Chemistry Keywords: COVID-19; protein protein interactions; virtual screening; docking; molecular dynamics; zinc

Online: 2 September 2020 (09:48:48 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202403.0473.v1

A tiny viral protein, SARS-CoV-2-ORF7b: Functional molecular mechanisms.

Gelsomina Mansueto, Giovanna Fusco, Giovanni Colonna

Subject: Biology And Life Sciences, Virology Keywords: SARS-CoV-2-ORF7b, COVID-19, Interactomics, Topological analysis, Cluster analysis, Co-regulation network, Transcription Factors, microRNA, SARS-CoV-2 inter-tissue diffusion, programmed death.

Online: 8 March 2024 (09:02:28 CET)

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Preprint ARTICLE | doi:10.20944/preprints202102.0588.v1

Inactivating SARS-CoV-2 Using 275nm UV-C LEDs through a Spherical Irradiation Box: Design, Characterization and Validation

Nicola Trivellin, Matteo Buffolo, Francesco Onelia, Alberto Pizzolato, Marco Barbato, Viviana Teresa Orlandi, Claudia Del Vecchio, Fabrizio Dughiero, Enrico Zanoni, Gaudenzio Meneghesso, Andrea Crisanti, Matteo Meneghini

Subject: Engineering, Automotive Engineering Keywords: SARS-CoV-2; Covid-19; LED; UVC; disinfection; inactivation; virucide

Online: 25 February 2021 (14:44:22 CET)

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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 ARTICLE | doi:10.20944/preprints202403.0923.v1

Seroprevalence of Anti-SARS-Cov-2 Antibodies among Patients Visiting Hospital-Based Sentinel Sites in the Rift Valley Region, Kenya

Vincent Kiplangat Ruttoh, Brian Kipkoech, Ronald Tonui, Ruth Omoti John, Ibrahim Ndungu Mwangi, Ruth Wambui Gicho, Sally Wambui Kamau, Maureen Wangui Njihia, Samwel Lifumo Symekher, Timothy Muasya Mwanzia, James Murithi Gikunda, Matthew Mutinda Munyao, Caroline Wangui Njoroge, Samson Muuo Nzou

Subject: Biology And Life Sciences, Virology Keywords: Seroprevalence; SARS-CoV-2; COVID-19; Vaccination; Antibodies

Online: 15 March 2024 (19:11:29 CET)

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Background: Accurate estimation of the spread of SARS-CoV-2 is crucial for guiding public health strategies. Underreporting from PCR-based testing, especially in low- and middle-income countries, often obscures the true extent of exposure and immunity to coronavirus disease 2019 (COVID-19). This study aimed to determine the seroprevalence and antibody levels against SARS-CoV-2 among patients visiting hospital-based sentinel sites in Kenya's Rift Valley region following the Omicron wave. Method: We conducted a cross-sectional study in four hospital-based sentinel sites among patients with acute respiratory infection symptoms. Patients aged six months or older visiting the sites between January 2022 and December 2022, presenting with symptoms of acute respiratory infection, were enrolled. Clinical and sociodemographic data were collected using a structured questionnaire. We used a quantitative ELISA kit to detect IgG antibodies against SARS-CoV-2 S protein in serum samples. Results: Among 557 individuals enrolled in the study, the seroprevalence of SARS-CoV-2 antibodies was 97.8% (n=545). Vaccinated individuals demonstrated significantly higher odds of seropositivity compared to unvaccinated counterparts, with an odds ratio of 3.33 (95% CI: (0.4, 27.87)). While seropositivity remained consistent across age groups, older adults exhibited the highest odds. Site-specific differences in enrolment and vaccination rates highlight potential access-related disparities. Conclusion: Our findings indicate widespread prior exposure to SARS-CoV-2 within the study region, underscoring the significant impact of both natural infection and vaccination efforts in driving SARS-CoV-2 seroprevalence within the Rift Valley region. Despite the underestimation of infections and disparities in vaccination access, this study demonstrates the effectiveness of vaccination for conferring SARS-CoV-2 immunity. Targeted interventions are crucial to address accessibility barriers and vaccine hesitancy, ensuring equitable vaccination coverage.

Preprint ARTICLE | doi:10.20944/preprints202301.0404.v1

XBB.1.5 Kraken Cracked: Gibbs Energies of Binding and Biosynthesis of the XBB.1.5 Variant of SARS-Cov-2

Marko Popovic

Subject: Biology And Life Sciences, Virology Keywords: Omicron variant; Infectivity; Pathogenicity; Biothermodynamics; COVID-19; Viral evolution

Online: 23 January 2023 (08:53:40 CET)

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Preprint BRIEF REPORT | doi:10.20944/preprints202105.0187.v1

Detection of Fecal SARS-CoV-2 RNA in a Prospective Cohort of Children with Multisystem Inflammatory Syndrome (MIS-C)

Emilia Parodi, Andrea Carpino, Elena Franchitti, Giulia Pruccoli, Marco Denina, Federica Pagliero, Ugo Ramenghi, Deborah Traversi

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: SARS-CoV-2; stools; COVID-19; MIS-C; children

Online: 10 May 2021 (13:00:43 CEST)

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Working Paper ARTICLE

Raising Concern About Cross-Infection Between Humans and Companion Animals by Evolutionary Analysis of Receptors for SARS-CoV-2

Huihao Tang, Mayan Ali, Lina Zhang, Cheng Deng

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: COVID-19; SARS-CoV-2; companion animals; cross-infection

Online: 17 May 2020 (15:27:24 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202404.0538.v1

Wastewater-Based Epidemiology for SARS-CoV-2 in Northern Italy: A Spatiotemporal Model

Matilde Fondriest, Lorenzo Vaccari, Federico Aldrovandi, Laura De Lellis, Filippo Ferretti, Carmine Fiorentino, Erica Mari, Maria Grazia Mascolo, Laura Minelli, Vincenza Perlangeli, Giuseppe Bortone, Paolo Pandolfi, Annamaria Colacci, Andrea Ranzi

Subject: Public Health And Healthcare, Public, Environmental And Occupational Health Keywords: Wastewater-based epidemiology; SARS-CoV-2; COVID-19; wastewater; biodegradation; sewer network; spatiotemporal model; public health; early-warning system

Online: 8 April 2024 (14:48:16 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202403.0572.v1

Link Between the G Protein-Coupled Receptor (GPCR), SARS-CoV-2 Spike Protein, ACE2, Vaccines, and Long COVID

Marcos Altable

Subject: Biology And Life Sciences, Neuroscience And Neurology Keywords: G Protein-Coupled Receptor; SARS-CoV-2 Spike (S) Protein; Vaccines; Long COVID; ACE2; COVID-19

Online: 11 March 2024 (05:33:53 CET)

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Preprint REVIEW | doi:10.20944/preprints202105.0549.v1

What Could Explain the Lower COVID-19 Burden in Africa Despite Considerable Circulation of the SARS-CoV-2 Virus?

Richard G. Wamai, Jason L. Hirsch, Wim Van Damme, David Alnwick, Robert C. Bailey, Stephen Hodgins, Uzma Alam, Mamka Anyona

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: COVID-19 pandemic; Africa; SARS-CoV-2 virus spread; lower COVID-19 disease burden; African populations; demographic pyramid; trained immunity; government measures

Online: 24 May 2021 (09:56:05 CEST)

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Preprint REVIEW | doi:10.20944/preprints202005.0029.v1

Thalidomide-Revisited: Are COVID-19 Patients Going to be the Latest Victims of Yet Another Theoretical Drug-Repurposing?

Athar khalil, Amina Kamar, Georges Nemer

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: COVID-19; Cytokine Storm; Lung Injury; Thalidomide; Anti-inflammatory Drug

Online: 3 May 2020 (07:31:53 CEST)

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Preprint REVIEW | doi:10.20944/preprints202401.1910.v1

Cytokine Storm Fatal Acute Kidney Infection Triggered by COVID-19 (SARS CoV-2) Infection: A Review

Hailemeleak Regassa, Kasahun Gudeta, Ankeet Bhagat, Rachna Chaturvedi

Subject: Medicine And Pharmacology, Internal Medicine Keywords: cytokine storm, COVID-19, Acute kidney infection, SARS-CoV-2, pro-inflammatory cytokines

Online: 29 January 2024 (02:10:24 CET)

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Preprint ARTICLE | doi:10.20944/preprints202306.2087.v1

SARS-CoV-2 and Influenza Vaccine Hesitancy during the COVID-19 Pandemic in a Dynamic Perspective

Valentina Gerussi, Maddalena Peghin, Alvisa Palese, Maria De Martino, Elena Graziano, Stefania Chiappinotto, Federico Fonda, Giulia Bontempo, Tosca Semenzin, Luca Martini, Miriam Isola, Carlo Tascini

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: Influenza; COVID-19; SARS-CoV-2; Green-Pass; Vaccination; Immunization; Vaccine-hesitancy; Pandemic

Online: 29 June 2023 (10:23:58 CEST)

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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.

Working Paper REVIEW

A Critical Review of Disinfection Processes to Control SARS-CoV-2 Transmission in the Food Industry

Adrián Pedreira, Yeşim Taşkın, Míriam R. García

Subject: Biology And Life Sciences, Food Science And Technology Keywords: SARS-CoV-2; COVID-19 pandemic; food industry; disinfection trade-offs; one-health

Online: 15 December 2020 (12:58:18 CET)

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Preprint ARTICLE | doi:10.20944/preprints202004.0439.v1

Highly Conserved Homotrimer Cavity Formed by the SARS-CoV-2 Spike Glycoprotein: A Novel Binding Site

Umesh Kalathiya, Monikaben Padariya, Marcos Mayordomo, Małgorzata Lisowska, Judith Nicholson, Ashita Singh, Maciej Baginski, Robin Fåhraeus, Neil Carragher, Kathryn Ball, Juergen Haas, Alison Daniels, Ted R. Hupp, Javier Antonio Alfaro

Subject: Biology And Life Sciences, Biophysics Keywords: SARS-CoV-2; COVID-19; spike glycoprotein; variability; molecular docking; molecular dynamics; inhibitors

Online: 24 April 2020 (11:42:01 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 ARTICLE | doi:10.20944/preprints202307.1994.v1

A Colorimetric RT-LAMP Detection of Multiple SARS-CoV-2 Variants of Concern and Lineages from Direct Nasopharyngeal Swab Samples without RNA Isolation

Santiago Enrique Werbajh, Luciana Larocca, Carolina Carrillo, Fabiana Stolowicz, Lorena Ogas, Sergio Pallotto, Solange Cassará, Lilia Mammana, Inés Zapiola, María Belén Bouzas, Adrián Alberto Vojnov

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

Online: 28 July 2023 (13:29:56 CEST)

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Preprint REVIEW | doi:10.20944/preprints202009.0420.v1

SARS-CoV-2 S Protein Binding hACE2: Viral Entry, Pathogenesis, Prognosis, and Potential Therapeutic Targets

Lobna Al-Zaidan, Sarra Mestiri, Afsheen Raza, Maysaloun Merhi, Varghese Inchakalody, Queenie Fernandez, Nassiba Taib, Shahab Uddin, Said Dermime

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: COVID-19; SARS-CoV-2; ACE2 receptor; spike glycoprotein; S glycoprotein immunogenic sequences; ACE2 polymorphism

Online: 18 September 2020 (04:56:02 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202401.1449.v1

COVID-19–Sensitive Tumour Response – 2-Year Assessment of the SARS-CoV-2 Humoral Response in Cancer Patients in Oncology Hospital in Poland

Piotr Kosiorek, Bożena Mikołuć, Samuel Stróż, Anna Hryniewicz, Dorota Elżbieta Kazberuk, Robert Milewski, Anna Grzeszczuk, Magdalena Joanna Borkowska, Anna Stasiak-Barmuta

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: breast cancer; lung cancer; colon cancer; SARS-CoV-2; COVID-19

Online: 19 January 2024 (04:45:55 CET)

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Background: So far, vaccination has been considered the most crucial defense against viral infection, including SARS-CoV-2. Numerous reports have demonstrated the effectiveness of the above vaccines in oncology patients. It has also been proven that, apart from vaccinations and oncological therapy, the course of the cancer process itself influences the magnitude of the humoral response, especially in people after infection with SARS-CoV-2. Objective: This study aimed to answer the question about the impact of the cancer process on the humoral response in oncological patients vaccinated against SARS-CoV-2 infection and in patients after COVID-19. Material and methods: 1,668 people were observed. Over two years, 5,082 SARS-CoV-2 IgG and IgM antibody samples were determined. The concentration of antibodies was assessed in three groups of oncological patients: those undergoing anticancer therapy after contracting COVID-19 and those after vaccination against the SARS-CoV-2 infection. Results: The obtained results indicate a naturally more significant humoral response in oncological patients who have not been vaccinated and have not undergone anticancer therapy, such as radiotherapy, chemotherapy, or surgical intervention. The above observation applies to patients with breast, lung, and colon cancer, although the response varies significantly depending on the type of cancer. Summary: The size of the humoral response and the presence of specific antibodies directed against the SARS-CoV-2, IgM, and IgG, in response to the supply of the vaccine antigen or assessed after COVID-19, is an indicator of adequate immune protection against reinfection. This study highlights for the first time the phenomenon of increased humoral response in response to a viral infection in patients with certain types of cancer that are assumed to be sensitive to oncological therapy, the initiation of which, according to generally accepted principles, was blocked by infection with the SARS-CoV-2. The phenomenon we observe seems to confirm the presence of a "natural" defence potential in a cancer patient's body, in this case, directed against infection with a viral pathogen. A "stronger" antiviral response also seems to explain the asymptomatic course of SARS-CoV-2 infection in some of the above patients. It remains an open question to what extent the SARS-CoV-2 infection weakened the "natural" potential of the anticancer response in these patients.

Preprint ARTICLE | doi:10.20944/preprints202104.0050.v1

Biological Cloth Face Coverings - The Reduction of SARS-CoV-2 and Influenza (H1N1) Infectivity by Viruferrin^TMTreatment

Emily Medina Magues, Anna Stedman, Paul Hope, Jorge E. Osorio

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: COVID-19; face masks; Personal Protective Equipment; Personal Protective Material; droplet; aerosols

Online: 2 April 2021 (11:28:19 CEST)

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Preprint ESSAY | doi:10.20944/preprints202012.0730.v1

Model Estimation for Sars-Cov-2 Peak Contagion (Mespc): Brazil’s Case for the First and Second Wave

Guilherme Asai

Subject: Computer Science And Mathematics, Algebra And Number Theory Keywords: Monte Carlo Simulation; Bayesian statistics; SARS-CoV-2; Covid-19; model estimation

Online: 29 December 2020 (14:34:24 CET)

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Preprint ARTICLE | doi:10.20944/preprints202012.0655.v1

SARS-CoV-2 and Rohingya Refugee Camp, Bangladesh: Uncertainty and How the Government Took Over the Situation

Md. Kamrujjaman, MD. Shahriar Mahmud, Shakil Ahmed, Md. Omar Qayum, Mohammad Morshad Alam, Md Nazmul Hassan, Md Rafiul Islam, Kaniz Fatema Nipa, Ummugul Bulut

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: COVID-19; Rohingya Refugee camp; Mathematical model; Numerical results; Basic reproduction number.

Online: 25 December 2020 (12:06:46 CET)

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Preprint REVIEW | doi:10.20944/preprints202205.0014.v2

SARS-CoV-2 infection and Diabetes: Pathophysiological Mechanism of Multi-System Organ Failure

Bipradas Roy, Sadia Afrin Runa

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: COVID-19; SARS-CoV-2; Diabetes; Neurological dysfunction; Cardiovascular complications; Pulmonary dysfunction; Renal dysfunction; bone loss; Eye disease; Gastrointestinal complications

Online: 23 May 2022 (11:00:06 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202003.0413.v1

Ontological and Bioinformatic Analysis of Anti-Coronavirus Drugs and Their Implication for Drug Repurposing against COVID-19

Yingtong Liu, Wallace K.B. Chan, Zhigang Wang, Junguk Hur, Jiangan Xie, Hong Yu, Yongqun He

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: coronavirus; drug; COVID-19; SARS; MERS; ontology; ChEBI; NDF-RT; DrON; bioinformatics

Online: 29 March 2020 (01:58:40 CET)

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

Preprint ARTICLE | doi:10.20944/preprints202310.1719.v2

Demographic Characteristics of Pre-Vaccinated Asymptomatic and Symptomatic SARS-CoV-2 Cases in Barwon South West Victoria, Australia

Shinae C Tobin-Salzman, Darcie Cooper, Bridgette J McNamara, Eugene Athan, Catherine M Bennett

Subject: Public Health And Healthcare, Public Health And Health Services Keywords: SARS-CoV-2; asymptomatic; COVID-19; symptom profile; demographic; testing; ethnicity

Online: 4 December 2023 (04:21:35 CET)

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Preprint ARTICLE | doi:10.20944/preprints202205.0247.v1

Description of a One-Year Succession of Variants of Interest and Concern of SARS-Cov-2 in Venezuela

Rossana C. Jaspe, Carmen L. Loureiro, Yoneira F. Sulbaran, Zoila C. Moros, Pierina D´Angelo, Mariana Hidalgo, Lieska Rodriguez, Victor Alarcon, Marwan Aguilar, Doneyla Sanchez, Jesus Ramirez, Domingo J. Garzaro, Jose Luis Zambrano, Ferdinando Liprandi, Hector Rafael Rangel, Flor H. Pujol

Subject: Biology And Life Sciences, Virology Keywords: COVID-19; SARS-CoV-2; Variants of Concern; Rapid screening; Mutations

Online: 19 May 2022 (03:31:36 CEST)

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Preprint REVIEW | doi:10.20944/preprints202004.0511.v1

COVID-19 Infection Diagnosis: Potential Impact of Isothermal Amplification Technology to Reduce Community Transmission of SARS-COV-2

Ameh S. James, John I. Al-alawneh

Subject: Public Health And Healthcare, Public Health And Health Services Keywords: point of care testing; novel coronavirus; COVID-19; rapid testing; LAMP

Online: 29 April 2020 (13:43:54 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202009.0154.v1

SARS-CoV-2 (COVID-19 Pandemic) in Nigeria: Multi-institutional Survey of Knowledge, Practices and Perception Amongst Undergraduate Veterinary Medical Students

Oluwawemimo Adebowale, Olubukola Adenubi, Hezekiah Adesokan, Abimbola Oloye, Noah Bankole, Oladotun Fadipe, Patience Ayo-Ajayi, Adebayo Akinloye

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: COVID-19; Knowledge; Practices; Perception; Veterinarians students; Nigeria

Online: 7 September 2020 (03:52:58 CEST)

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Background: The novel Coronavirus SARS-CoV-2 (COVID-19) is a global pandemic with an increasing public health concern. Due to the non-availability of a vaccine against the disease, non-pharmaceutical interventions constitute major preventive and control measures. However, inadequate knowledge about the disease and poor perception might limit compliance. Aim: This study examined COVID-19-related knowledge, practices, perceptions and associated factors amongst undergraduate veterinary medical students in Nigeria. Methods: A cross-sectional web survey was employed to collect data from 437 consenting respondents using pre-tested self-administered questionnaire (August 2020). Demographic factors associated with the knowledge and adoption of recommended preventive practices towards COVID-19 were explored using multivariate logistic regression at P ≤ 0.05.Results: The respondents’ mean knowledge and practice scores were 22.7 (SD ± 3.0) and 24.1 (SD ± 2.9), respectively with overall 63.4% and 88.8% displaying good knowledge and satisfactory practice levels. However, relatively lower proportions showed adherence to avoid touching face or nose (19.5%), face mask-wearing (58.1%), and social distancing (57.4%). Being in the 6^th year of study (OR = 3.18, 95%CI: 1.62-6.26, P = 0.001) and female (OR = 2.22, 95% CI = 1.11-4.41, P = 0.024) were significant positive predictors of good knowledge and satisfactory practices, respectively. While only 30% of the respondents perceived the pandemic as a scam or a disease of the elites (24.0%), the respondents were worried about their academics being affected negatively (55.6%). Conclusion: The study revealed good knowledge and satisfactory preventive practices towards COVID-19 among Nigerian Veterinary students; albeit with essential gaps in the key non-pharmaceutical preventive measures recommended by the WHO. Therefore, there is a need to step up enlightenment and targeted campaigns about COVID-19 pandemic.

Preprint ARTICLE | doi:10.20944/preprints202005.0022.v1

Structural and Genetic Analysis of Coronaviruses Spike Proteins Suggest Pangolin as a Proximate Intermediate Host of SARS-CoV-2 (COVID-19)

Sohail Raza, Muhammad Asif Rasheed, Wajeeha Zahir, Muhammad Tariq Navid, Rana Aamir Diwan, Muhammad Awais, Tahir Yaqub, Masood Rabbani, Muhammad Rashid

Subject: Biology And Life Sciences, Virology Keywords: COVID-19; SARS-CoV-2; origin; bat; pangolin

Online: 2 May 2020 (16:29:38 CEST)

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Preprint REVIEW | doi:10.20944/preprints202004.0075.v1

SARS-CoV-2/COVID-19 and Advances in Developing Potential Therapeutics and Vaccines to Counter this Emerging Pandemic Virus – A Review

Ali A. Rabaan, Shamsah H. Al-Ahmed, Ranjit Sah, Ruchi Tiwari, Mohd. Iqbal Yatoo, Shailesh Kumar Patel, Mamta Pathak, Yashpal Singh Malik, Kuldeep Dhama, Karam Pal Singh, D. Katterine Bonilla-Aldana, Shafiul Haque, Alfonso J. Rodriguez-Morales

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: SARS-CoV-2; COVID-19; immunotherapeutics; therapeutics; vaccines

Online: 7 April 2020 (02:01:34 CEST)

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

Preprint ARTICLE | doi:10.20944/preprints202104.0534.v1

AuNP Coupled Rapid Flow-Through Dot-Blot Immuno-Assay for COVID-19 (SARS-CoV-2) Explicit IgG Antibody Revelation

Bijon Kumar Sil, Mohd. Raeed Jamiruddin, Md. Ahsanul Haq, Mohib Ullah Khondoker, Nowshin Jahan, Shahad Saif Khandker, Tamanna Ali, Mumtarin Jannat Oishee, Taku Kaitsuka, Masayasu Mie, Kazuhito Tomizawa, Eiry Kobatake, Mainul Haque, Nihad Adnan

Subject: Biology And Life Sciences, Virology Keywords: COVID-19, SARS-CoV-2, Serological test, Sensitivity, Specificity, Serosurveillance.

Online: 20 April 2021 (11:36:09 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202104.0439.v1

One Possible Reinfection with SARS-CoV-2 Validated by 205-days Interval of Re-detection in Sapporo City, Japan

Toshiaki Asakura, Akiko Tamakoshi

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: SARS-CoV-2; COVID-19; reinfection; re-detected positive; Japan

Online: 16 April 2021 (11:09:45 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202310.1684.v1

High Exposure to SARS-CoV-2 among Pregnant Women after the First and Second Waves of COVID-19 in Senegal

Abou Abdallah Malick Diouara, Fatou Thiam, Seynabou Coundoul, Noël Magloire Manga, Halimatou Diop Ndiaye, Assane Senghor, Sophie Deli Tene, Sarbanding Sané, Betty Kane, Habibou Sarr, Yakhya Dieye, Seynabou Lo, Fodé Danfakha, Marie Edouard Faye Dieme, Babacar Biaye, Cheikh Momar Nguer, Martine Peeters, Coumba TOURE KANE, Ahidjo Ayouba

Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: SARS-CoV-2; Seroprevalence; Pregnancy and COVID-19; Senegal

Online: 26 October 2023 (09:09:00 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202102.0078.v1

Inactivation of Human Coronavirus by Fathhome’s Dry Sanitizer Device: Rapid and Eco-friendly Ozone-based Disinfection of SARS-CoV-2

Timsy Uppal, Amir Khazaieli, Antoine Snijders, Subhash C. Verma

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: FATHHOME, SARS-CoV-2; COVID-19; Virus decontamination, PPEs

Online: 2 February 2021 (09:34:25 CET)

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Preprint ARTICLE | doi:10.20944/preprints202007.0251.v1

RNA-Dependent RNA Polymerase and Spike Protein Mutant Variants of SARS-CoV-2 Predominate in Severely Affected COVID-19 Patients

Subrata K. Biswas, Sonchita R. Mudi

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: SARS-CoV-2; COVID-19; Spike protein; Mutant; Genome

Online: 12 July 2020 (12:03:16 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202204.0008.v1

KERRA, Mixed Medicinal Plant Extracts, Inhibits SARS-CoV-2 Targets Enzymes and Feline Corona Virus

Supaphorn Seetaha, Phatcharin Khamplong, Panatda Wanaragthai, Thitinan Aiebchun, Siriluk Ratanabunyong, Sucheewin Krobthong, Yodying Yingchutrakul, Jatuporn Rattanasrisomporn, Kiattawee Choowongkomon

Subject: Medicine And Pharmacology, Pharmacy Keywords: COVID-19 pandemic; KERRA; SARS-CoV-2 main protease; RNA-dependent RNA polymerase; anti-FIPV activity

Online: 1 April 2022 (14:53:44 CEST)

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Preprint HYPOTHESIS | doi:10.20944/preprints202005.0177.v1

Interference of SARS-CoV-2 with the Homeostasis of Ventilation and Perfusion in the Lung

Clemente F. Arias, Francisco J. Acosta, Federica Bertocchini, Cristina Fernández-Arias

Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: SARS-CoV-2; COVID-19; homeostasis; hypoxic pulmonary vasoconstriction; renin-angiotensin system; hydrostatic edema; permeability edema

Online: 10 May 2020 (17:22:59 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202309.0576.v1

Neutralization of Different Variants of SARS-CoV-2 by a F(ab’)2 Preparation from Sera of Horses Immunized with the Viral Receptor Binding Domain

Mariajosé Rodriguez-Nuñez, Mariana del Valle Cepeda, Carlos Bello, Miguel Angel Lopez, Yoneira Sulbaran, Carmen Luisa Loureiro, Ferdinando Liprandi, Rossana Celeste Jaspe, Héctor Rafael Rangel, Flor Helene Pujol

Subject: Biology And Life Sciences, Virology Keywords: COVID-19; variants; equine sera; neutralizing antibodies; immune escape; evolution

Online: 8 September 2023 (09:37:59 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202403.0192.v1

Correlating Quantitative and Genomic SARS-CoV-2 Wastewater Data with Clinical Metrics in Metropolitan Perth, Western Australia

Jake Gazeley, Terence Lee, Daniel R Knight, Alexander Shivarev, Cameron Gordon, David Speers, Dylan D Barth, Jelena Maticevic, Meredith Hodge, Paul Armstrong, Paul Knight, Sandra Sjollema, Avram Levy

Subject: Public Health And Healthcare, Public Health And Health Services Keywords: Wastewater-based epidemiology; SARS-CoV-2; COVID-19; surveillance system; correlation analysis; genomics

Online: 5 March 2024 (09:07:35 CET)

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Preprint ARTICLE | doi:10.20944/preprints202306.0871.v1

María Gónzalez, Miriam Al-Adib, Ana Beatriz Rodríguez, Cristina Carrasco

Subject: Public Health And Healthcare, Public, Environmental And Occupational Health Keywords: women’s health; COVID-19 vaccine; menstrual-related disturbances; formerly menstruating women; secondary amenorrhea

Online: 13 June 2023 (03:38:41 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/preprints202004.0161.v2

High Throughput Virtual Screening to Discover Inhibitors of the Main Protease of the Coronavirus SARS-CoV-2

Olujide O. Olubiyi, Maryam Olagunju, Monika Keutmann, Jennifer Loschwitz, Birgit Strodel

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: COVID-19; docking; drug repurposing; natural products; in silico drug design; viral replication inhibition

Online: 1 June 2020 (02:42:54 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202307.1790.v1

Humoral Response to Dengue Virus Infections Potentiates Antibody-Dependent Enhancement of SARS-CoV-2

Guilherme C Lechuga, Jairo R Temerozo, Paloma Napoleão-Pêgo, Dumit C Bou-Habib, Carlos M Morel, David W Provance-Jr, Thiago M.L. Souza, Salvatore Giovanni De-Simone

Subject: Biology And Life Sciences, Virology Keywords: Spike protein; B-cell epitope mapping; COVID-19; DENV; SARS-CoV-2 variants; Vaccination; Cross-reactivity; Antibody-mediated enhancement.

Online: 26 July 2023 (09:41:31 CEST)

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Working Paper REVIEW

Immunogenicity of Clinically Relevant SARS-CoV-2 Vaccines in Non-human Primates and Humans

P.J. Klasse, D. F. Nixon, J. P. Moore

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: SARS-CoV-2; S-protein; RBD; COVID-19; neutralizing antibodies; serology; T-cells; vaccines; animal models; Operation Warp Speed

Online: 27 October 2020 (11:25:32 CET)

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Preprint ARTICLE | doi:10.20944/preprints202005.0199.v1

Revealing SARS-CoV-2 Functional Druggability Through Multi-Target Cadd Screening of Repurposable Drugs

Yash Gupta, Dawid Maciorowski, Raman Mathur, Catherine M. Pearce, David J. Ilc, Hamza Husein, Ajay Bharti, Daniel Becker, Rathi Brijesh, Steven B Bradfute, Ravi Durvasula, Prakasha Kempaiah

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: SARS-CoV-2; COVID-19; CADD; virtual screening; approved drugs; drug repurposing; essential targets; molecular docking; molecular dynamics simulations

Online: 11 May 2020 (13:14:18 CEST)

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The emergence of SARS/MERS drug resistant COVID-19 with high transmission and mortality has recently been declared a deadly pandemic causing economic chaos and significant health problems. Like all coronaviruses, SARS-CoV-2 is a large virus that has many druggable components within its proteome. In this study, we focused on repurposing approved and investigational drugs by identifying potential drugs that are predicted to effectively inhibit critical enzymes within SARS-CoV-2. We shortlisted seven target proteins with enzymatic activities known to be essential at different stages of the virus life cycle. For virtual screening, the energy minimization of a crystal structure or modeled protein was carried out using Protein Preparation Wizard (Schrödinger LLC, 2020-1). Following active site selection based on data mining and COACH predictions, we performed a high-throughput virtual screen of drugs (n=5903) that are already approved by worldwide regulatory bodies including the FDA, using the ZINC database. Screening was performed against viral targets using three sequential docking modes (i.e. HTVS, SP and XP). Our in-silico virtual screening identified ~290 potential drugs based on the criteria of energy, docking parameters, ligand and binding site strain and score. Drugs specific to each target protein were further analyzed for binding free energy perturbation by molecular mechanics (prime MM-GBSA) and pruning the hits to the top 32 candidates. A top lead from each target group was further subjected to molecular dynamics simulation (MDS) using the Desmond module to validate the efficacy of the screening pipeline. All of the simulated hit-target complexes were predicted to strongly interact and with highly stable binding. Thus, we have identified a number of approved and investigational drugs with high likelihood of inhibiting a variety of key SARS-CoV-2 proteins. Follow-up studies will continue to identify inhibitors suitable for combination therapy based on drug-drug synergy to thwart resistance. In addition, the screening hits that we have identified provide excellent probes for understanding the binding properties of the active sites of all seven targets, further enabling us to derive consensus molecules through computer-aided drug design (CADD). While infections are expanding at a rampant pace, it must be recognized that resistance will grow commensurately through either genetic shift and/or genetic drift to all small molecule drugs identified. Vaccines should provide a more permanent solution through prevention, but resistivity is still a possible scenario. Nevertheless, a persistent multi-target drug development program is essential to curb this ongoing pandemic and to keep reemergence in check.

Preprint ARTICLE | doi:10.20944/preprints202203.0040.v1

Augmented Sensitivity of At-Home Rapid SARS-CoV-2 Antigen Test (RAT) Kits with Computer Vision

Kim Miikki, Lars Miikki, Jenny Wiklund, Alp Karakoç

Subject: Biology And Life Sciences, Virology Keywords: SARS-CoV-2; rapid antigen test; RT-PCR test; COVID-19; image processing; Raspberry Pi

Online: 2 March 2022 (08:06:49 CET)

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Preprint ARTICLE | doi:10.20944/preprints202101.0473.v1

Summarize of the Available Molecular Methods for Detection of Sars-Cov-2 During the Ongoing Pandemic

Fabio Arena, Simona Pollini, Gian Maria Rossolini, Maurizio Margaglione

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: molecular methods; virus; pandemic; Coronaviridae; COVID-19, diagnosis; UK variant; B.1.1.7 variant; 501Y.V2 variant

Online: 25 January 2021 (10:32:38 CET)

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Preprint REVIEW | doi:10.20944/preprints202306.0508.v1

Pathological Effects of SARS-CoV-19 Associated With Hematological Abnormalities

Mrs Shama, Asif Mahmood, Shahid Mehmood, Wen Zhang

Subject: Public Health And Healthcare, Public Health And Health Services Keywords: SARS-CoV-2; Hematology; COVID-19; Biomarkers

Online: 7 June 2023 (08:05:43 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202402.1094.v1

Development and Evaluation of an In-House Real-Time Rt-Pcr Targeting nsp10 Gene for SARS-CoV-2 Detection

Cyril Chik-Yan Yip, Jane Hau-Ching Poon, Kit-Hang Leung, Wan-Mui Chan, Jonathan Daniel Ip, Allen Wing-Ho Chu, Vincent Chi-Chung Cheng, Kwok-Yung Yuen, Kelvin Kai-Wang To

Subject: Biology And Life Sciences, Virology Keywords: SARS-CoV-2; COVID-19; nsp10; real-time RT-PCR; diagnostic

Online: 20 February 2024 (06:07:31 CET)

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Preprint REVIEW | doi:10.20944/preprints202310.0001.v2

Xenosialylation: Role in SARS/CoV-2 Post-infectious and Post-vaccination Complications and Common Cause of Hyperimmune/Autoimmune Diseases

Fiorella Carnevali, Sara Mangiaterra, Giacomo Rossi

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: sialic acid; sialylation; xeno-sialic acid; COVID-19; SARS-CoV-2

Online: 14 December 2023 (05:56:10 CET)

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The host glycosylation mechanism synthesizes the carbohydrates of glycoproteins of viral envelopes. Due to the loss of the Cytidine Monophospho-N-Acetylneuraminic Acid Hydroxylase gene by some mammalian species, including humans (negative-CMAH), Neu5Gc is no longer synthesized. Uptake of Neu5Gc by negative-CMAH species, through the intake of food products derived from positive-CMAH mammals, leads to incorporating Neu5Gc-glycans in the glycocalyx (xenosialylation). Neu5Gc, being a Mammalian-associated Carbohydrate Antigen (MCA), acts as a non-self-antigen, inducing an inflammatory reaction (Xenosialitis), and triggering the production of circulating antiNeu5Gc antibodies to attack/remove all incorporated Neu5Gc. In the state of Xenosialitis, the virus-neutralizing antibodies produced by a heavily xenosialylated patient following exposure to viral infection (including SarsCoV2) or anti SarsCoV2 vaccination cross-react against all incorporated non-self Neu5Gc-MCA glycans due to their resemblance with viral envelope antigens synthesized by the host glycosylation mechanism. In addition, the circulating anti-XeSias antibodies determine the massive removal of the circulating neutralizing FC-xeno-contaminated antibodies by the serum, living only the hyper-inflammatory agalattosylated antiviral IgG antibodies. Therefore, we hypothesize that the combination of antibody cross-reaction against non-self Neu5Gc-MCA glycans and the massive removal of the xeno-contaminated newly formed neutralizing antibodies in favor of hyper reactive antibodies, could be the cause of the massive inflammatory reaction (cytokine storm, coagulopathies, neuropathies) observed in Covid 19 patients or after anti-SarsCoV2 vaccination. This analysis is an invitation to investigate the post-infectious and/or post-vaccination adverse phenomena in the light of xenosialization as a key to understanding the severe post viral and post vaccine complications, including SARS-CoV2 infection or related vaccination.

Preprint ARTICLE | doi:10.20944/preprints202008.0530.v1

Antiviral phytochemicals identified in Rhododendron arboreum petals exhibited strong binding to SARS-CoV-2 M^Pro and Human ACE2 receptor

Maneesh Lingwan, Shagun Shagun, Yogesh Pant, Bandna Kumari, Ranjan Nanda, Shyam K Masakapalli

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: R. arboreum, Antiviral phytochemicals, SARS-CoV-2, MPro, ACE2, COVID-19

Online: 24 August 2020 (11:14:07 CEST)

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Background: Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) affects human respiratory function causing COVID-19 disease. Safe natural products with potential antiviral phytochemicals with benefits to control high-altitude sickness could be adopted as adjunct therapy for COVID-19. The red petals of Rhododendron arboreum, commonly available and consumed in the Himalayan region may have phytochemicals with potential antiviral properties against COVID-19 targets.Purpose: This study was aimed to profile the secondary metabolites of R. arboreum petals, to assess their absorption, distribution, metabolism and elimination (ADME) properties and evaluate their antiviral potential by docking against COVID-19 targets such as SARS-CoV-2 main protease (M^pro PDB ID: 6LU7) and Human Angiotensin Converting Enzyme 2 (ACE2) receptor (PDB ID: 1R4L) that mediates the viral replication and entry into the host respectively.Methods: The phytochemicals of R. arboreum petals were mainly profiled using Gas Chromatography-Mass Spectroscopy (GC-MS) and ¹H-NMR. In addition, the phytochemicals reported from the literature were tabulated. The ADME properties of the phytochemicals were predicted using SwissADME tool. Molecular docking simulation of the phytochemicals against SARS-CoV-2 main protease (M^pro PDB ID: 6LU7) and Human Angiotensin converting enzyme 2 (ACE2) receptor (PDB ID: 1R4L) were carried out using PyRx.Results: R. arboreum petals were found to be rich in appreciable proportions of secondary metabolites such as Quinic acid, 3-Caffeoyl-quinic acid, 5-O-Coumaroyl-D-quinic acid, 5-O-Feruloylquinic acid, 2,4-Quinolinediamine, Coumaric acid, Caffeic acid, Epicatechin, Catechin, 3-Hydroxybenzoic acid, Shikimic acid, Protocatechuic acid, Epicatechin gallate, Quercetin, Quercetin-O-pentoside, Quercetin-O-rhamnoside, Kaempferol-O-pentoside and Kaempferol. Several of these phytochemicals were reported to exhibit inhibitory activities against a range of viruses. From the molecular docking studies, 5-O-Feruloylquinic acid, 3-Caffeoyl-quinic acid, 5-O-Coumaroyl-D-quinic acid, Epicatechin and Catechin showed strong binding affinity with SARS-CoV-2 M^pro and human ACE2 receptor.Conclusion: This report showed that R. arboreum petals are rich in several antiviral phytochemicals that also docked against SARS-CoV-2 M^Pro and Human ACE2 receptor. This is the first report highlighting R. arboreum petals as a reservoir of antiviral phytochemicals with potential for synergetic activities. The outcomes merit further in vitro, in vivo and clinical studies on R. arboreum phytochemicals to develop natural formulations against COVID-19 disease for therapeutic benefits.

Preprint REVIEW | doi:10.20944/preprints202007.0262.v1

Epidemiological Models of SARS-CoV-2 (COVID-19) to Control the Transmission Based on Current Evidence: A Systematic Review

Swati Arora, Rishabh Jain, Harendra Pal Singh

Subject: Public Health And Healthcare, Health Policy And Services Keywords: SARS-COV-2; COVID-19; Lockdown; Epidemiological Models; Machine Learning; Transmission

Online: 12 July 2020 (15:18:48 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202309.0139.v4

A Recombinant Protein XBB.1.5 RBD/Alum/CpG Vaccine Elicits High Neutralizing Antibody Titers against Omicron Subvariants of SARS-CoV-2

Syamala Rani Thimmiraju, Rakesh Adhikari, Maria J Villar, Jungsoon Lee, Zhuyun Liu, Rakhi Kundu, Yi-Lin Chen, Suman Sharma, Karm Ghei, Brian Keegan, Leroy Versteeg, Portia M Gillespie, Allan Ciciriello, Nelufa Yesmin, Cristina Poveda, Nestor Uzcategui, Wen-Hsiang Chen, Jason T Kimata, Bin Zhan, Ulrich Strych, Maria Elena Bottazzi, Peter Hotez, Jeroen Pollet

Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: Immune escape; Vaccine efficacy; COVID-19; SARS-CoV-2

Online: 30 September 2023 (07:44:51 CEST)

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Working Paper ARTICLE

Ancestral Area Reconstruction of SARS-CoV-2 Indicates Multiple Sources of Entry into Australia

Ngoc Minh Hien Phan, Helen Faddy, Robert Flower, Kirsten Spann, Eileen Roulis

Subject: Biology And Life Sciences, Virology Keywords: SARS-CoV-2; COVID-19; novel severe acute respiratory syndrome coronavirus 2; ancestral reconstruction; clonality; source of entry; dispersal routes

Online: 28 June 2020 (09:21:49 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202004.0084.v1

In silico Repositioning for Dual Inhibitor Discovery of SARS-CoV-2 (COVID-19) 3C-like Protease and Papain-like Peptidase

Kowsar Bagherzadeh, Kourosh Daneshvarnejad, Mohammad Abbasinazari, homa azizian

Subject: Chemistry And Materials Science, Medicinal Chemistry Keywords: in silico repositioning; dual inhibitor; Covid-19; 3CLpro; PLpro; remdesivir

Online: 7 April 2020 (10:44:11 CEST)

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Preprint COMMUNICATION | doi:10.20944/preprints202311.1268.v1

The Naturally Occurring m¹A RNA Modification Can Be Efficiently Incorporated into RNA by SARS-CoV-2 RdRp

Alexander Apostle, Reed Arneson, Yinan Yuan, Shiyue Fang

Subject: Biology And Life Sciences, Life Sciences Keywords: SARS-CoV-2; COVID-19; RdRp; m¹A triphosphate; Antiviral Drug

Online: 21 November 2023 (07:19:23 CET)

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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/preprints202004.0063.v1

A Proposal for Isotherm World Maps to Forecast the Seasonal Evolution of the SARS-CoV-2 Pandemic

Nicola Scafetta

Subject: Biology And Life Sciences, Virology Keywords: SARS-CoV-2; COVID-19; Pandemic geographical distribution; Epidemic forecasting; Weather conditions; Climatic zones.

Online: 6 April 2020 (14:11:52 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202206.0410.v1

Patients with Inflammatory Bowel Disease on anti-Tumor Necrosis Factor Therapy Might be Predisposed to SARS-CoV-2 Variants Infection Even after Receiving a Third mRNA Vaccine Dose

Paola López-Marte, Alondra Soto-González, Lizzie Ramos-Tollinchi, Stephan Torres-Jorge, Mariana Ferre, Esteban Rodríguez-Martinó, Esther A. Torres, Carlos A. Sariol

Subject: Medicine And Pharmacology, Gastroenterology And Hepatology Keywords: COVID-19 variants; COVID-19 vaccine; IBD; ulcerative colitis; Crohn’s disease; anti-TNF

Online: 29 June 2022 (15:02:36 CEST)

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Preprint TECHNICAL NOTE | doi:10.20944/preprints202008.0659.v1

Noisy Genome Data and Faulty Clade Statistics Undermine Conclusions on SARS-CoV-2 Evolution and Strain Typing in the Brazilian Epidemy: A Technical Note

Marcelo R. S. Briones, Fernando Antoneli, Renata C. Ferreira, Isabel M. V. G. Carvalho, Luiz M. R. Janini

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

Online: 30 August 2020 (11:22:12 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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Preprint ARTICLE | doi:10.20944/preprints202402.0240.v1

Detection of SARS-CoV-2 in Wastewater Associated with Scientific Stations in Antarctica and Possible Risk for Wildlife

Marcelo González-Aravena, Cristobal Galban-Malagon, Eduardo Castro-Nallar, Gonzalo P. Barriga, Victor Neira, Lucas Krüger, Aiko D. Adell, Jorge Olivares-Pacheco

Subject: Biology And Life Sciences, Virology Keywords: SARS-CoV-2; Antarctica; wastewater-based epidemiology; COVID-19; Antarctic wildlife; environmental surveillance

Online: 5 February 2024 (07:58:31 CET)

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Preprint ARTICLE | doi:10.20944/preprints202009.0486.v1

A Meta-analysis of Comorbidities in COVID-19: Which Diseases increase the Susceptibility of SARS-CoV-2 Infection?

Srinivasan Ramachandran, Manoj Kumar Singh, Ahmed Mobeen, Amit Chandra, Sweta Joshi

Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: COVID-19; comorbidity; SARS-CoV-2; leukemia; NAFLD; psoriasis; cancer; type II diabetes

Online: 21 September 2020 (03:32:58 CEST)

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Background: Comorbidities have been frequently reported in COVID-19 patients, which often lead to more severe outcomes. The underlying molecular mechanisms behind these clinical observations have not yet been explained. Herein, we investigated the disease-specific gene expression signatures that may induce susceptibility to SARS-CoV-2 infection. Methods: We studied 30 frequently occurring acute, chronic, or infectious diseases of recent times that have shown comorbidity in one or another respiratory disease(s) caused by pathogenic human infecting coronaviruses, especially SARS-CoV-2. We retrieved array-based gene expression data for each disease and control from relevant datasets. Subsequently, all the datasets were quantile normalized, and log-2 transformed data was used for analysis. Results The expression of ACE2 receptor and host proteases, namely FURIN and TMPRSS2 that are essential for cellular entry of SARS-CoV-2, was upregulated in all six studied subtypes of leukemia (hereafter, referred as leukemia). The expression of ACE2 was also increased in psoriasis, lung cancer, Non-alcoholic fatty liver disease (NAFLD), breast cancer, and pulmonary arterial hypertension patients. The expression of FURIN was higher in psoriasis, NAFLD, lung cancer, and in type II diabetic liver, whereas it was lowered in breast cancer. Similarly, the expression of TMPRSS2 was increased during lung cancer and type II diabetes; it was decreased during psoriasis, NAFLD, lung cancer, breast cancer, and cervical cancer.Furthermore, a heightened expression of genes that are involved in immune response was observed in leukemia patients, as shown by the higher expression of IFNA2, IFNA8, IFNA10, IFNA14, IFNA16, IFNA21, IFNB1, CXCL10, and IL6. The expression of JAK1, STAT1, IL6, and CXCL10 was higher in NAFLD. Besides, JAK1 and STAT1 were upregulated in type II diabetic muscles. In addition, most of the upregulated genes in COVID-19 patients showed a similar trend in leukemia, NAFLD, and psoriasis. Furthermore, SARS-CoV-2, SARS-CoV and MERS CoV, were found to commonly alter two genes, namely, CARBONIC ANHYDRASE 11 and CLUSTERIN.Conclusions: The genes that may confer susceptibility to SARS-CoV-2 infection are mostly upregulated in leukemia patients; hence, leukemia patients are relatively more susceptible to develop COVID-19, followed by other chronic disorders, such as, NAFLD, type II diabetes, psoriasis, and hypertension. This study identifies key genes that are altered in the studied diseases types, which may aid in the infection of SARS-CoV-2 and underlie COVID-19 associated comorbidities.

Preprint ARTICLE | doi:10.20944/preprints202209.0328.v1

SARS-Cov-2 in Asymptomatic and Mild Infections in a Hungarian Outpatient Cohort in the First Year of the Pandemic

István Jankovics, Cecília Müller, Éva Gönczöl, Ildikó Visontai, István Varga, Márta Lőrincz, Dávid Kuti, Ágnes Hasitz, Péter Malik, Krisztina Ursu, Borbála Bányász, Júlia Sarkadi, Béla Dénes

Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: SARS-CoV-2; COVID-19; outpatient cohort; seroprevalence; mild infections; asymptomatic cases; COVID-19 contacts; PCR-positivity and symptoms; first year of the pandemic; Hungary

Online: 22 September 2022 (02:08:09 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202205.0243.v1

A Comparative Analysis of a Self-Reported Adverse Events Analysis After Receiving one of the Available SARS-CoV-2 Vaccine Schemes in Ecuador

Esteban Ortiz-Prado, Juan Sebastian Izquiero-Condoy, Raul Fernandez-Naranjo, Katherine Simbana-Rivera, Jorge Eduardo Vasconez, Eddy P Lincango-Naranjo, Simone Cordovez, Barbara Coronel, Karen Delgado-Moreira, Ruth Jimbo-Sotomayor

Subject: Public Health And Healthcare, Public Health And Health Services Keywords: COVID-19; Vaccines; Adverse Events; Self-reporting; Pandemic

Online: 18 May 2022 (11:06:19 CEST)

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The COVID-19 pandemic has put a lot of pressure on health systems worldwide. Mass vaccination against SARS-CoV-2 has reduced morbidity and mortality worldwide. Despite their safety profiles, vaccines like any other medical product can cause adverse events. Yet, in countries with poor epidemiological surveillance and monitoring systems, reporting vaccine-related adverse events is scarce. The objective of this study was to describe self-reported vaccine adverse events after receiving one of the available COVID-19 vaccine schemes in Ecuador. A cross-sectional analysis based on an online self-reporting 32-questionnaire was conducted in Ecuador from April 1st to July 15th, 2021. Participants were invited by social media, radio, and TV to voluntarily participate in our study. A total of 6,654 participants were included in this study. A 38.2% of the participants reported having at least one comorbidity. Patients received AstraZeneca, Pfizer, and Sinovac vaccines, and these were distributed 38.4%, 31.1%, and 30.5%, respectively. Pain, inflammation at the injection site (20,01%), and headache (16,91%) were the most reported adverse events. Women addressed ESAVIs (64%), more often than men (36%). After receiving the first dose of any available COVID-19 vaccine, a total of 19,481 self-reported ESAVIs were informed (86.9% were mild, 11.6% moderate and 1.5% severe). In terms of vaccine type and brand, the most reactogenic vaccine was AstraZeneca with 57.8%, followed by Pfizer (24.9%) and Sinovac (17, 3 %). After the second dose, 6,757 self-reported ESAVIs were reported (87.0% mild, 10.9% moderate, and 2.1% severe). AstraZeneca vaccine users reported a higher proportion of ESAVIs (72.2%) in comparison to Pfizer/BioNTech (15.9%) and Sinovac Vaccine (11.9%). Swelling at the injection site, headache, muscle pain, and fatigue were the most common ESAVIs for the first as well as second dose. In conclusion, most ESAVIs were mild. AstraZeneca users were more likely to report adverse events. Participants without a history of COVID-19 infection, as well as those who receive the first dose, were more prone to report ESAVIs.

Preprint ARTICLE | doi:10.20944/preprints202007.0189.v1

Is Japan Succeeding in Suppressing COVID-19? Estimation of Infection Rate and the Size of the Population Potentially Exposed to SARS-CoV-2

Motohiko Naito

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: SARS-CoV-2; COVID-19; NESID; Japan; infection

Online: 9 July 2020 (12:18:46 CEST)

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Preprint REVIEW | doi:10.20944/preprints202203.0338.v1

COVID-19 Test Frequency Versus Test Sensitivity in Disrupting SARS-CoV-2 Transmission: A Review of Statistical Modeling Simulations

Justin Rogers, Laurel Jackson, Adam Buss, Susan Gawel

Subject: Computer Science And Mathematics, Probability And Statistics Keywords: COVID-19; rapid testing; test sensitivity; test frequency; testing programs; compartmental models

Online: 25 March 2022 (03:50:14 CET)

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Preprint ARTICLE | doi:10.20944/preprints202004.0171.v2

Systems Biology Approach to Characterize Potential SARS-CoV-2 Pathways Based on Protein Functional Motifs

Haitham Sobhy

Subject: Biology And Life Sciences, Virology Keywords: protein functional domains; short linear motifs; coronaviruses; COVID-19; severe acute respiratory syndrome-related coronavirus; 2019-nCoV; virus outbreak

Online: 16 May 2020 (18:54:17 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202304.0961.v1

Whole Genome Sequence Analysis of SARS-COV-2 Isolated from COVID-19 Patients in Duhok Province, Iraq

Sherzad Majeed Taher, Jassim Mohammed Abdo, Muayad Aghali Merza

Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: COVID-19 patient; whole Genome sequence; Of SARS-COV-2; phylogenetic analysis and Transmission supported

Online: 26 April 2023 (05:15:36 CEST)

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Preprint REVIEW | doi:10.20944/preprints202005.0299.v1

A First Review to Explore the Association of Air Pollution (PM and NO₂) on Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2)

Chiara Copat, Antonio Cristaldi, Maria Fiore, Alfina Grasso, Pietro Zuccarello, Gea Oliveri Conti, Salvatore Santo Signorelli, Margherita Ferrante

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: air pollution; particulate matter; nitrogen dioxide; COVID-19; pandemic

Online: 18 May 2020 (09:36:25 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.

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