Coagulation modifiers targeting SARS-CoV-2 main protease Mpro for COVID-19 treatment: an in silico approach

Mem Inst Oswaldo Cruz. 2020:115:e200179. doi: 10.1590/0074-02760200179. Epub 2020 Jun 1.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection depends on viral polyprotein processing, catalysed by the main proteinase (Mpro). The solution of the SARS-CoV-2 Mpro structure allowed the investigation of potential inhibitors. This work aims to provide first evidences of the applicability of commercially approved drugs to treat coronavirus disease-19 (COVID-19). We screened 4,334 compounds to found potential inhibitors of SARS-CoV-2 replication using an in silico approach. Our results evidenced the potential use of coagulation modifiers in COVID-19 treatment due to the structural similarity of SARS-CoV-2 Mpro and human coagulation factors thrombin and Factor Xa. Further in vitro and in vivo analysis are needed to corroborate these results.

MeSH terms

  • Betacoronavirus*
  • COVID-19 Drug Treatment
  • Computer Simulation
  • Coronavirus 3C Proteases
  • Coronavirus Infections / drug therapy
  • Cysteine Endopeptidases
  • Humans
  • Protease Inhibitors / chemistry*
  • SARS-CoV-2
  • Structure-Activity Relationship
  • Viral Nonstructural Proteins / antagonists & inhibitors*

Substances

  • Protease Inhibitors
  • Viral Nonstructural Proteins
  • Cysteine Endopeptidases
  • Coronavirus 3C Proteases