Progress on SARS-CoV-2 3CLpro Inhibitors: Inspiration from SARS-CoV 3CLpro Peptidomimetics and Small-Molecule Anti-Inflammatory Compounds

Drug Des Devel Ther. 2022 Apr 8:16:1067-1082. doi: 10.2147/DDDT.S359009. eCollection 2022.

Abstract

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) currently poses a threat to human health. 3C-like proteinase (3CLpro) plays an important role in the viral life cycle. Hence, it is considered an attractive antiviral target protein. Whole-genome sequencing showed that the sequence homology between SARS-CoV-2 3CLpro and SARS-CoV 3CLpro is 96.08%, with high similarity in the substrate-binding region. Thus, assessing peptidomimetic inhibitors of SARS-CoV 3CLpro could accelerate the development of peptidomimetic inhibitors for SARS-CoV-2 3CLpro. Accordingly, we herein discuss progress on SARS-CoV-2 3CLpro peptidomimetic inhibitors. Inflammation plays a major role in the pathophysiological process of COVID-19. Small-molecule compounds targeting 3CLpro with both antiviral and anti-inflammatory effects are also briefly discussed in this paper.

Keywords: 3CLpro; SARS-CoV; SARS-CoV-2; anti-inflammatory agents; peptidomimetics; protease inhibitors; small-molecule inhibitors.

Publication types

  • Review

MeSH terms

  • Anti-Inflammatory Agents / pharmacology
  • Antiviral Agents* / pharmacology
  • COVID-19 Drug Treatment*
  • Coronavirus 3C Proteases* / antagonists & inhibitors
  • Humans
  • Peptidomimetics* / pharmacology
  • Protease Inhibitors* / chemistry
  • Protease Inhibitors* / pharmacology
  • SARS-CoV-2

Substances

  • Anti-Inflammatory Agents
  • Antiviral Agents
  • Peptidomimetics
  • Protease Inhibitors
  • 3C-like proteinase, SARS-CoV-2
  • Coronavirus 3C Proteases

Grants and funding

1. Supported by the opening foundation of the State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, grant NO. SKLID2020KF042.2. Supported by the Major horizontal project of Zhejiang Shuren University, grant NO. KHJ1720234.