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

• Published in: Pathogens (Basel) 2020-04, Vol.9 (5), p.320
• Main Authors: Neogi, Ujjwal, Hill, Kyle J, Ambikan, Anoop T, Heng, Xiao, Quinn, Thomas P, Byrareddy, Siddappa N, Sönnerborg, Anders, Sarafianos, Stefan G, Singh, Kamal
• Format: Article
• Language: English
• Subjects: coronavirus; COVID-19; MERS-CoV; RNA polymerase; SARS-CoV; SARS-CoV-2
• ISSN: 2076-0817; 2076-0817
• DOI: 10.3390/pathogens9050320

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.