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,*
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)
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.
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Keywords:
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.
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