Design, synthesis, and biological evaluation of dithiocarbamate derivatives as SARS-CoV-2 Mpro inhibitors

Bioorg Med Chem Lett. 2024 Dec 1:114:130011. doi: 10.1016/j.bmcl.2024.130011. Epub 2024 Oct 30.

Abstract

SARS-CoV-2 continues to mutate, spread, and impact public health and daily life. The main protease (Mpro) is essential for the replication and maturation of SARS-CoV-2, making it an ideal target for anti-coronaviral drug discovery and development due to its high conservation and lack of homologous proteases in humans. Herein, we designed and synthesized a series of dithiocarbamate derivatives as potent SARS-CoV-2 Mpro inhibitors. Notably, compound L2 exhibited an IC50 value of 9.1 ± 2.0 nM against SARS-CoV-2 Mpro, underscoring its potential as a promising candidate for anti-coronaviral therapy and justifying further research and development.

Keywords: Dithiocarbamates derivatives; Drug design; Main protease; SARS-CoV-2.

MeSH terms

  • Antiviral Agents* / chemical synthesis
  • Antiviral Agents* / chemistry
  • Antiviral Agents* / pharmacology
  • COVID-19 Drug Treatment
  • Coronavirus 3C Proteases* / antagonists & inhibitors
  • Coronavirus 3C Proteases* / metabolism
  • Drug Design*
  • Humans
  • Molecular Docking Simulation
  • Molecular Structure
  • Protease Inhibitors / chemical synthesis
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / pharmacology
  • SARS-CoV-2* / drug effects
  • Structure-Activity Relationship
  • Thiocarbamates* / chemical synthesis
  • Thiocarbamates* / chemistry
  • Thiocarbamates* / pharmacology

Substances

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