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2000
Volume 32, Issue 28
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X

Abstract

Background/Aim

The global pandemic caused by the novel SARS-CoV-2 virus underscores the urgent need for therapeutic interventions. Targeting the virus's main protease (Mpro), crucial for viral replication, is a promising strategy.

Objective

The current study aims to discover novel inhibitors of Mpro.

Methods

The current study identified five natural compounds (myrrhanol B (), myrrhanone B (), catechin (), quercetin (), and feralolide () with strong inhibitory potential against Mpro through virtual screening and computational methods, predicting their binding efficiencies and validated it using the inhibition activity. The selected compound's toxicity was examined using the MTT assay on a human BJ cell line.

Results

Compound exhibited the highest binding affinity, with a docking score of -9.82 kcal/mol and strong hydrogen bond interactions within Mpro's active site. A microscale molecular dynamics simulation confirmed the stability and tight fit of the compounds in the protein's active pocket, showing superior binding interactions. assays validated their inhibitory effects, with having the most significant potency (IC = 2.85 µM). The non-toxic nature of these compounds in human BJ cell lines was also confirmed, advocating their safety profile.

Conclusion

These findings highlight the effectiveness of combining computational and experimental approaches to identify potential lead compounds for SARS-CoV-2, with emerging as promising candidates for further drug development against this virus.

© 2025 Bentham Science Publishers
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2024-04-05
2025-09-11

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Discovery of Novel Natural Inhibitors against SARS-CoV-2 Main Protease: A Rational Approach to Antiviral Therapeutics
Curr. Med. Chem. 32, 5973 (2025); https://doi.org/10.2174/0109298673292839240329081008
/content/journals/cmc/10.2174/0109298673292839240329081008
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  • Article Type:     Research Article
Keyword(s): docking; enzyme inhibition assay; MM-GBSA; molecular dynamic simulation; Natural products; toxicity

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