Related Experiment Video

Updated: Oct 21, 2025

Pharmacophore Modeling for Targets with Extensive Ligand Libraries: A Case Study on SARS-CoV-2 Mpro
05:50

Pharmacophore Modeling for Targets with Extensive Ligand Libraries: A Case Study on SARS-CoV-2 Mpro

Published on: September 26, 2025

248

Discovery of novel inhibitors of SARS-CoV-2 main protease

Lei Zheng1, Yanmei Chen1, Jingxiao Bao1

  • 1Shanghai Engineering Research Center of Molecular Therapeutics & New Drug Development, Shanghai Key Laboratory of Green Chemistry & Chemical Process, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, China.

Journal of Biomolecular Structure & Dynamics
|September 2, 2021
PubMed

Insights

Researchers identified four novel compounds that inhibit the Mpro enzyme, a key target for treating COVID-19. The best compounds show promising low toxicity and potential for developing new anti-SARS-CoV-2 drugs.

Area of Science:

  • Biochemistry
  • Drug Discovery
  • Computational Chemistry

Background:

  • COVID-19 is an infectious disease caused by SARS-CoV-2.
  • The Mpro enzyme is a critical target for COVID-19 therapeutics.
  • Existing research primarily focuses on drug repurposing for Mpro inhibition.

Purpose of the Study:

  • To screen for novel Mpro inhibitors using computational methods.
  • To identify compounds with high inhibitory activity and low cell toxicity.
  • To provide a foundation for developing new anti-SARS-CoV-2 drugs.

Main Methods:

  • Computational free energy calculations were employed.
  • A compound library was screened against the Mpro target.
  • Inhibitor-Mpro interactions were analyzed through detailed decomposition.

Main Results:

  • Four novel Mpro-inhibiting compounds were discovered.
  • The top two compounds (AG-690/13507628 and AG-690/13507724) exhibited IC50 values under 3 μM.
  • These lead compounds demonstrated low cellular toxicity.

Conclusions:

  • The identified compounds represent promising candidates for further anti-SARS-CoV-2 drug development.
  • Understanding key interactions aids in designing more effective inhibitors.
  • This study offers a basis for future therapeutic strategies against COVID-19.
Keywords:
COVID-19inhibitory activitymain proteasevirtual screening

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