A review on the interaction of nucleoside analogues with SARS-CoV-2 RNA dependent RNA polymerase

Int J Biol Macromol. 2021 Jun 30:181:605-611. doi: 10.1016/j.ijbiomac.2021.03.112. Epub 2021 Mar 22.

Abstract

The outbreaks of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) in 2019, have highlighted the concerns about the lack of potential vaccines or antivirals approved for inhibition of CoVs infection. SARS-CoV-2 RNA dependent RNA polymerase (RdRp) which is almost preserved across different viral species can be a potential target for development of antiviral drugs, including nucleoside analogues (NA). However, ExoN proofreading activity of CoVs leads to their protection from several NAs. Therefore, potential platforms based on the development of efficient NAs with broad-spectrum efficacy against human CoVs should be explored. This study was then aimed to present an overview on the development of NAs-based drug repurposing for targeting SARS-CoV-2 RdRp by computational analysis. Afterwards, the clinical development of some NAs including Favipiravir, Sofosbuvir, Ribavirin, Tenofovir, and Remdesivir as potential inhibitors of RdRp, were surveyed. Overall, exploring broad-spectrum NAs as promising inhibitors of RdRp may provide useful information about the identification of potential antiviral repurposed drugs against SARS-CoV-2.

Keywords: Antiviral; COVID-19; Drug; Nucleoside analogue; SARS-CoV-2.

Publication types

  • Review

MeSH terms

  • Adenosine Monophosphate / analogs & derivatives
  • Adenosine Monophosphate / pharmacology
  • Alanine / analogs & derivatives
  • Alanine / pharmacology
  • Antiviral Agents / pharmacology
  • COVID-19 / virology
  • COVID-19 Drug Treatment*
  • Computational Biology / methods
  • Drug Repositioning / methods
  • Humans
  • Models, Molecular
  • Nucleosides / pharmacology*
  • RNA-Dependent RNA Polymerase / antagonists & inhibitors
  • RNA-Dependent RNA Polymerase / metabolism*
  • SARS-CoV-2 / drug effects*
  • SARS-CoV-2 / enzymology*

Substances

  • Antiviral Agents
  • Nucleosides
  • remdesivir
  • Adenosine Monophosphate
  • RNA-Dependent RNA Polymerase
  • Alanine