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Pathogens
Volume 9
Issue 5
10.3390/pathogens9050320
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Article

Feasibility of Known RNA Polymerase Inhibitors as Anti-SARS-CoV-2 Drugs

by
Ujjwal Neogi
1,2,†,
Kyle J. Hill
2,3,†,
Anoop T Ambikan
1,
Xiao Heng
4,
Thomas P. Quinn
4,
Siddappa N. Byrareddy
5,
Anders Sönnerborg
2,3,6,
Stefan G. Sarafianos
7 and
Kamal Singh
1,2,3,8,*
1
Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, 14186 Stockholm, Sweden
2
Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, MO 65211, USA
3
Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USA
4
Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA
5
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Centre, Omaha, NE 68198, USA
6
Division of Infectious Diseases, Department of Medicine Huddinge, Karolinska Institute, 14186 Stockholm, Sweden
7
Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA
8
Shift Pharmaceuticals, Overland Park, KS 66211, USA
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this manuscript.
Pathogens 2020, 9(5), 320; https://doi.org/10.3390/pathogens9050320
Received: 3 April 2020 / Revised: 23 April 2020 / Accepted: 24 April 2020 / Published: 26 April 2020
(This article belongs to the Section Human Pathogens)
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Abstract

Coronaviruses (CoVs) are positive-stranded RNA viruses that infect humans and animals. Infection by CoVs such as HCoV-229E, -NL63, -OC43 and -HKU1 leads to the common cold, short lasting rhinitis, cough, sore throat and fever. However, CoVs such as Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and the newest SARS-CoV-2 (the causative agent of COVID-19) lead to severe and deadly diseases with mortality rates ranging between ~1 to 35% depending on factors such as age and pre-existing conditions. Despite continuous global health threats to humans, there are no approved vaccines or drugs targeting human CoVs, and the recent outbreak of COVID-19 emphasizes an urgent need for therapeutic interventions. Using computational and bioinformatics tools, here we present the feasibility of reported broad-spectrum RNA polymerase inhibitors as anti- SARS-CoV-2 drugs targeting its main RNA polymerase, suggesting that investigational and approved nucleoside RNA polymerase inhibitors have potential as anti-SARS-CoV-2 drugs. However, we note that it is also possible for SARS-CoV-2 to evolve and acquire drug resistance mutations against these nucleoside inhibitors. View Full-Text
Keywords: coronavirus; SARS-CoV; MERS-CoV; SARS-CoV-2; COVID-19; RNA polymerase; nsp12 coronavirus; SARS-CoV; MERS-CoV; SARS-CoV-2; COVID-19; RNA polymerase; nsp12
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MDPI and ACS Style

Neogi, U.; Hill, K.J.; Ambikan, A.T.; Heng, X.; Quinn, T.P.; Byrareddy, S.N.; Sönnerborg, A.; Sarafianos, S.G.; Singh, K. Feasibility of Known RNA Polymerase Inhibitors as Anti-SARS-CoV-2 Drugs. Pathogens 2020, 9, 320. https://doi.org/10.3390/pathogens9050320

AMA Style

Neogi U, Hill KJ, Ambikan AT, Heng X, Quinn TP, Byrareddy SN, Sönnerborg A, Sarafianos SG, Singh K. Feasibility of Known RNA Polymerase Inhibitors as Anti-SARS-CoV-2 Drugs. Pathogens. 2020; 9(5):320. https://doi.org/10.3390/pathogens9050320

Chicago/Turabian Style

Neogi, Ujjwal, Kyle J. Hill, Anoop T. Ambikan, Xiao Heng, Thomas P. Quinn, Siddappa N. Byrareddy, Anders Sönnerborg, Stefan G. Sarafianos, and Kamal Singh. 2020. "Feasibility of Known RNA Polymerase Inhibitors as Anti-SARS-CoV-2 Drugs" Pathogens 9, no. 5: 320. https://doi.org/10.3390/pathogens9050320

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