Non-Nucleotide RNA-Dependent RNA Polymerase Inhibitor That Blocks SARS-CoV-2 Replication

Viruses. 2021 Aug 11;13(8):1585. doi: 10.3390/v13081585.


SARS-CoV-2 has caused an extensive pandemic of COVID-19 all around the world. Key viral enzymes are suitable molecular targets for the development of new antivirals against SARS-CoV-2 which could represent potential treatments of the corresponding disease. With respect to its essential role in the replication of viral RNA, RNA-dependent RNA polymerase (RdRp) is one of the prime targets. HeE1-2Tyr and related derivatives were originally discovered as inhibitors of the RdRp of flaviviruses. Here, we present that these pyridobenzothiazole derivatives also significantly inhibit SARS-CoV-2 RdRp, as demonstrated using both polymerase- and cell-based antiviral assays.

Keywords: COVID-19; RNA-dependent RNA polymerase; SAR-CoV-2; antiviral agents; non-nucleotide inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Monophosphate / analogs & derivatives
  • Adenosine Monophosphate / pharmacology
  • Alanine / analogs & derivatives
  • Alanine / pharmacology
  • Animals
  • Antiviral Agents / pharmacology*
  • Benzothiazoles / pharmacology*
  • Cell Line
  • Cell Survival / drug effects
  • Coronavirus RNA-Dependent RNA Polymerase / antagonists & inhibitors*
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Microbial Sensitivity Tests
  • Pyridones / pharmacology*
  • SARS-CoV-2 / drug effects*
  • SARS-CoV-2 / enzymology
  • SARS-CoV-2 / physiology
  • Virus Replication / drug effects*


  • Antiviral Agents
  • Benzothiazoles
  • Enzyme Inhibitors
  • HeE1-2Tyr
  • Pyridones
  • remdesivir
  • Adenosine Monophosphate
  • Coronavirus RNA-Dependent RNA Polymerase
  • NSP12 protein, SARS-CoV-2
  • Alanine