Prediction of Small Molecule Inhibitors Targeting the Severe Acute Respiratory Syndrome Coronavirus-2 RNA-dependent RNA Polymerase

Mohammed Ahmad; Abhisek Dwivedy; Richard Mariadasse; Satish Tiwari; Deepsikha Kar; Jeyaraman Jeyakanthan; Bichitra K Biswal

doi:10.1021/acsomega.0c02096

Prediction of Small Molecule Inhibitors Targeting the Severe Acute Respiratory Syndrome Coronavirus-2 RNA-dependent RNA Polymerase

ACS Omega. 2020 Jul 14;5(29):18356-18366. doi: 10.1021/acsomega.0c02096. eCollection 2020 Jul 28.

Authors

Mohammed Ahmad¹, Abhisek Dwivedy¹, Richard Mariadasse², Satish Tiwari¹, Deepsikha Kar¹, Jeyaraman Jeyakanthan², Bichitra K Biswal¹

Affiliations

¹ National Institute of Immunology, New Delhi 110067, India.
² Department of Bioinformatics, Alagappa University, karaikudi 630004, Tamil Nadu, India.

Abstract

The current COVID-19 outbreak warrants the design and development of novel anti-COVID therapeutics. Using a combination of bioinformatics and computational tools, we modelled the 3D structure of the RdRp (RNA-dependent RNA polymerase) of SARS-CoV2 (severe acute respiratory syndrome coronavirus-2) and predicted its probable GTP binding pocket in the active site. GTP is crucial for the formation of the initiation complex during RNA replication. This site was computationally targeted using a number of small molecule inhibitors of the hepatitis C RNA polymerase reported previously. Further optimizations suggested a lead molecule that may prove fruitful in the development of potent inhibitors against the RdRp of SARS-CoV2.