Unveiling the mechanism of action of a novel natural dual inhibitor of SARS-CoV-2 Mpro and PLpro with molecular dynamics simulations
2025

New Natural Inhibitors for SARS-CoV-2 Proteases

publication 10 minutes Evidence: high

Author Information

Author(s): Gu Xiaoxia, Zhang Xiaotian, Zhang Xueke, Wang Xinyu, Sun Weiguang, Zhang Yonghui, Hu Zhengxi

Primary Institution: Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology

Hypothesis

Can sydowiol B and violaceol I effectively inhibit SARS-CoV-2 Mpro and PLpro?

Conclusion

Sydowiol B and violaceol I are promising dual inhibitors of SARS-CoV-2 proteases with broad-spectrum antiviral activity.

Supporting Evidence

  • Sydowiol B and violaceol I showed dual inhibitory activity against SARS-CoV-2 Mpro and PLpro.
  • Sydowiol B exhibited IC50 values of 2.91 µM for Mpro and 5.77 µM for PLpro.
  • Both compounds displayed broad-spectrum antiviral activity against homologous coronaviruses.
  • Sydowiol B binding stabilizes the Mpro dimer and limits substrate accommodation.

Takeaway

Researchers found two natural compounds, sydowiol B and violaceol I, that can help stop the virus that causes COVID-19 by blocking important parts of the virus.

Methodology

The study used molecular dynamics simulations and high-throughput screening to evaluate the inhibitory effects of sydowiol B and violaceol I on SARS-CoV-2 proteases.

Digital Object Identifier (DOI)

10.1007/s13659-024-00486-4

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