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Evaluating the potential of different inhibitors on RNA-dependent RNA polymerase of severe acute respiratory syndrome coronavirus 2: A molecular modeling approach.

Authors
  • Choudhury, Shuvasish1
  • Moulick, Debojyoti2
  • Saikia, Purbajyoti3
  • Mazumder, Muhammed Khairujjaman3
  • 1 Assistant Professor (Life Science & Bioinformatics), Assam University, Silchar, Assam 788011, India. , (India)
  • 2 Research Associate, Central Instrumentation Laboratory, Assam University, Silchar, Assam 788011, India. , (India)
  • 3 Assistant Professor (Zoology), Dhemaji College, Dhemaji, Assam 787057, India. , (India)
Type
Published Article
Journal
Medical Journal Armed Forces India
Publisher
Elsevier
Publication Date
Jul 01, 2021
Volume
77
Identifiers
DOI: 10.1016/j.mjafi.2020.05.005
PMID: 32836709
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Coronavirus disease 2019 (COVID-19) has already affected 2883603 and killed 198842 people, as of April 27, 2020. Because there is no specific therapeutic drug, drug repurposing has been proposed. RNA-dependent RNA polymerase (RdRp) is a promising drug against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to control its replication, and several compounds have been suggested. The present study predicts relative efficacies of thirty known or repurposed compounds in inhibiting the RdRp. The three-dimensional structure of the target enzyme was loaded into Molegro virtual docker software, followed by chemical structures of the test compounds. The docking was performed between the compounds and the active site of the enzyme to determine docking scores, and the energy liberated when the two dock. Thus, docking scores signify the affinity of ligand(s) with the active site of enzyme(s) and thus its inhibitory potential. Among known inhibitors, remdesivir was found to have the highest affinity for the active site of the RdRp. Among all compounds, chlorhexidine was predicted as the most potent inhibitor. Furthermore, the results predict the relative efficacy of different drugs as inhibitors of the drug target. While the study identifies several compounds as inhibitors of RdRp of SARS-CoV-2, the prediction of their relative efficacies may be useful in future studies. While nucleoside analogs compete with the natural substrate of RdRp, thereby terminating RNA replication, other compounds would physically block entry of the natural substrates into the active site. Thus, based on the findings, we recommend in vitro and in vivo studies and clinical trials to determine their effectiveness against COVID-19. © 2020 Director General, Armed Forces Medical Services. Published by Elsevier, a division of RELX India Pvt. Ltd.

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