Preprint Article Version 1 This version is not peer-reviewed

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

Version 1 : Received: 11 April 2020 / Approved: 12 April 2020 / Online: 12 April 2020 (05:36:40 CEST)

How to cite: 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. Preprints 2020, 2020040184 (doi: 10.20944/preprints202004.0184.v1). 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. Preprints 2020, 2020040184 (doi: 10.20944/preprints202004.0184.v1).

Abstract

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

Subject Areas

Coronavirus; SARS-CoV; MERS-CoV; SARS-CoV-2; COVID-19; RNA polymerase; nsp12

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