Repurposing Nimesulide, a Potent Inhibitor of the B0AT1 Subunit of the SARS-CoV-2 Receptor, as a Therapeutic Adjuvant of COVID-19

SLAS Discov. 2020 Dec;25(10):1171-1173. doi: 10.1177/2472555220934421. Epub 2020 Jun 5.

Abstract

The global pandemic caused by the SARS-CoV-2 infection is a health emergency that needs to be addressed immediately. The international scientific community, following World Health Organization (WHO) indications, launched different trials for testing drugs putatively able to block the SARS-CoV-2 infection or treat the COVID-19 disease symptoms. In parallel, studies devoted to a better understanding of SARS-CoV-2 biology are in the course for designing an effective vaccine. One of the human membrane proteins known to be docked by the virus is angiotensin-converting enzyme 2 (ACE2), proposed to be responsible for viral entry in target cells. Recently, the 3D structure of ACE2 has been obtained, showing its physical interaction with B0AT1 (SLC6A19), a plasma membrane transporter involved in the trafficking of amino acids in cells. The receptor targeted by SARS-CoV-2 is a supercomplex formed by a dimer of ACE2-B0AT1, in which ACE2 binds the viral protein and B0AT1 stabilizes the heterodimer. As a serendipity occurrence, nimesulide was shown to abolish the transport function of B0AT1. Here we suggest including nimesulide in the list of drugs to be tested for the identification of co-adjuvants in the treatment of COVID-19.

Keywords: ACE2-B0AT1; COVID-19; SARS-CoV-2; SLC6A19; drug discovery; nimesulide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Transport Systems, Neutral / chemistry
  • Amino Acid Transport Systems, Neutral / metabolism*
  • Angiotensin-Converting Enzyme 2 / chemistry
  • Angiotensin-Converting Enzyme 2 / metabolism
  • Antiviral Agents / pharmacology*
  • COVID-19 Drug Treatment
  • Drug Repositioning
  • Host-Pathogen Interactions / drug effects
  • Humans
  • SARS-CoV-2 / pathogenicity*
  • Serine Endopeptidases / metabolism
  • Sulfonamides / pharmacology*

Substances

  • Amino Acid Transport Systems, Neutral
  • Antiviral Agents
  • SLC6A19 protein, human
  • Sulfonamides
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • Serine Endopeptidases
  • TMPRSS2 protein, human
  • nimesulide