Recent Advances in SARS-CoV-2 Main Protease Inhibitors: From Nirmatrelvir to Future Perspectives

Biomolecules. 2023 Sep 2;13(9):1339. doi: 10.3390/biom13091339.

Abstract

The main protease (Mpro) plays a pivotal role in the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is considered a highly conserved viral target. Disruption of the catalytic activity of Mpro produces a detrimental effect on the course of the infection, making this target one of the most attractive for the treatment of COVID-19. The current success of the SARS-CoV-2 Mpro inhibitor Nirmatrelvir, the first oral drug for the treatment of severe forms of COVID-19, has further focused the attention of researchers on this important viral target, making the search for new Mpro inhibitors a thriving and exciting field for the development of antiviral drugs active against SARS-CoV-2 and related coronaviruses.

Keywords: COVID-19; Paxlovid; SARS-CoV-2 Mpro; coronavirus; nirmatrelvir; peptidomimetics; protease inhibitors.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents* / chemistry
  • Antiviral Agents* / pharmacology
  • Antiviral Agents* / therapeutic use
  • COVID-19 Drug Treatment*
  • Coronavirus 3C Proteases* / antagonists & inhibitors
  • Coronavirus 3C Proteases* / chemistry
  • Coronavirus 3C Proteases* / metabolism
  • Humans
  • Lactams
  • Leucine / analogs & derivatives
  • Leucine / pharmacology
  • Nitriles
  • Proline / analogs & derivatives
  • Proline / pharmacology
  • Protease Inhibitors* / chemistry
  • Protease Inhibitors* / pharmacology
  • Protease Inhibitors* / therapeutic use
  • SARS-CoV-2* / drug effects
  • SARS-CoV-2* / enzymology

Substances

  • Coronavirus 3C Proteases
  • Antiviral Agents
  • Protease Inhibitors
  • nirmatrelvir
  • Leucine
  • Proline
  • Lactams
  • Nitriles