Inhibition of the predicted allosteric site of the SARS-CoV-2 main protease through flavonoids.

Bibi Kubra, Syed Lal Badshah, Shah Faisal, Mohamed Sharaf, Abdul-Hamid M. Emwas, Mariusz Jaremko, Mohnad Abdalla

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Since its emergence in 2019, coronavirus infection (COVID-19) has become a global pandemic and killed several million people worldwide. Even though several types of vaccines are available against the COVID-19 virus, SARS-CoV-2, new strains are emerging that pose a constant danger to vaccine effectiveness. In this computational study, we identified and predicted potent allosteric inhibitors of the SARS-CoV-2 main protease (Mpro). Via molecular docking and simulations, more than 100 distinct flavonoids were docked with the allosteric site of Mpro. Docking experiments revealed four top hit compounds (Hesperidin, Schaftoside, Brickellin, and Marein) that bound strongly to the Mpro predicted allosteric site. Simulation analyses further revealed that these continually interacted with the enzyme's allosteric region throughout the simulation time. ADMET and Lipinski drug likenesses were calculated to indicate the therapeutic value of the top four hits: They were non-toxic and exhibited high human intestinal absorption concentrations. These novel allosteric site inhibitors provide a higher chance of drugging SARS-CoV2 Mpro due to the rapid mutation rate of the viral enzyme's active sites. Our findings provide a new avenue for developing novel allosteric inhibitors of SARS-CoV-2 Mpro.
Original languageEnglish (US)
Pages (from-to)1-18
Number of pages18
JournalJournal of biomolecular structure & dynamics
StatePublished - Nov 20 2022

Bibliographical note

KAUST Repository Item: Exported on 2022-11-29
Acknowledgements: The author(s) reported there is no funding associated with the work featured in this article.

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology


Dive into the research topics of 'Inhibition of the predicted allosteric site of the SARS-CoV-2 main protease through flavonoids.'. Together they form a unique fingerprint.

Cite this