Evaluation of Xa inhibitors as potential inhibitors of the SARS-CoV-2 Mpro protease

PLoS One. 2022 Jan 11;17(1):e0262482. doi: 10.1371/journal.pone.0262482. eCollection 2022.

Abstract

Based on previous large-scale in silico screening several factor Xa inhibitors were proposed to potentially inhibit SARS-CoV-2 Mpro. In addition to their known anticoagulants activity this potential inhibition could have an additional therapeutic effect on patients with COVID-19 disease. In this study we examined the binding of the Apixaban, Betrixaban and Rivaroxaban to the SARS-CoV-2 Mpro with the use of the MicroScale Thermophoresis technique. Our results indicate that the experimentally measured binding affinity is weak and the therapeutic effect due to the SARS-CoV-2 Mpro inhibition is rather negligible.

MeSH terms

  • Benzamides / chemistry
  • Benzamides / metabolism
  • Binding Sites
  • COVID-19 / virology
  • COVID-19 Drug Treatment
  • Coronavirus M Proteins / antagonists & inhibitors*
  • Coronavirus M Proteins / metabolism
  • Factor Xa Inhibitors / chemistry*
  • Factor Xa Inhibitors / metabolism
  • Humans
  • Molecular Dynamics Simulation
  • Protein Binding
  • Protein Stability
  • Pyrazoles / chemistry
  • Pyrazoles / metabolism
  • Pyridines / chemistry
  • Pyridines / metabolism
  • Pyridones / chemistry
  • Pyridones / metabolism
  • Rivaroxaban / chemistry
  • Rivaroxaban / metabolism
  • SARS-CoV-2 / isolation & purification
  • SARS-CoV-2 / metabolism*

Substances

  • Benzamides
  • Coronavirus M Proteins
  • Factor Xa Inhibitors
  • Pyrazoles
  • Pyridines
  • Pyridones
  • membrane protein, SARS-CoV-2
  • apixaban
  • betrixaban
  • Rivaroxaban

Grants and funding

KP, PS, PK, MB, AG - Plastic Omnium Auto Sp. z o.o. for support of the experimental part of this work. AF, MS1, MAL, MS2 - NVIDIA Corporation with the donation of a Titan Xp GPU used for this research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.