Targeting SARS-CoV-2 Polymerase with New Nucleoside Analogues

Molecules. 2021 Jun 7;26(11):3461. doi: 10.3390/molecules26113461.

Abstract

Despite the fact that COVID-19 vaccines are already available on the market, there have not been any effective FDA-approved drugs to treat this disease. There are several already known drugs that through drug repositioning have shown an inhibitory activity against SARS-CoV-2 RNA-dependent RNA polymerase. These drugs are included in the family of nucleoside analogues. In our efforts, we synthesized a group of new nucleoside analogues, which are modified at the sugar moiety that is replaced by a quinazoline entity. Different nucleobase derivatives are used in order to increase the inhibition. Five new nucleoside analogues were evaluated with in vitro assays for targeting polymerase of SARS-CoV-2.

Keywords: COVID-19; nucleoside derivatives; quinazoline moiety.

MeSH terms

  • Antiviral Agents / chemical synthesis*
  • Chemistry, Pharmaceutical / methods
  • Coronavirus RNA-Dependent RNA Polymerase / antagonists & inhibitors*
  • Drug Design*
  • Enzyme Inhibitors / chemical synthesis*
  • In Vitro Techniques
  • Nucleosides / analogs & derivatives*
  • Nucleosides / chemical synthesis*
  • SARS-CoV-2 / drug effects
  • SARS-CoV-2 / enzymology*

Substances

  • Antiviral Agents
  • Enzyme Inhibitors
  • Nucleosides
  • Coronavirus RNA-Dependent RNA Polymerase