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

Pathogens

Xiao Heng¹  Thomas P. Quinn¹  Anders Sönnerborg²  Kyle J. Hill²  Siddappa N. Byrareddy³  Anoop T Ambikan⁴  Kamal Singh⁴  Ujjwal Neogi⁴  Stefan G. Sarafianos⁵ 

[1] Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA;Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, MO 65211, USA;Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Centre, Omaha, NE 68198, USA;Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, 14186 Stockholm, Sweden;Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA;

关键词: coronavirus;    SARS-CoV;    MERS-CoV;    SARS-CoV-2;    COVID-19;    RNA polymerase;   

DOI  :  10.3390/pathogens9050320

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown