Molecules (Nov 2022)

Isolation and In Silico Prediction of Potential Drug-like Compounds with a New Dimeric Prenylated Quinolone Alkaloid from <i>Zanthoxylum rhetsa</i> (Roxb.) Root Extracts Targeted against SARS-CoV-2 (Mpro)

  • Fatema Tuz Zohora,
  • A. T. M. Zafrul Azam,
  • Sinthyia Ahmed,
  • Khondaker Miraz Rahman,
  • Mohammad A. Halim,
  • Md. Rafi Anwar,
  • Md. Hossain Sohrab,
  • Fatema Tabassum,
  • Choudhury Mahmood Hasan,
  • Monira Ahsan

DOI
https://doi.org/10.3390/molecules27238191
Journal volume & issue
Vol. 27, no. 23
p. 8191

Abstract

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A new dimeric prenylated quinolone alkaloid, named 2,11-didemethoxy-vepridimerine A, was isolated from the root bark of Zanthoxylum rhetsa, together with twelve known compounds. The structure of the new compound was elucidated on the basis of spectroscopic investigations (NMR and Mass). The interaction of the isolated compounds with the main protease of SARS-CoV-2 (Mpro) was evaluated using molecular docking followed by MD simulations. The result suggests that 2,11-didemethoxy-vepridimerine A, the new compound, has the highest negative binding affinity against the Mpro with a free energy of binding of −8.5 Kcal/mol, indicating interaction with the Mpro. This interaction was further validated by 100 ns MD simulation. This implies that the isolated new compound, which can be employed as a lead compound for an Mpro-targeting drug discovery program, may be able to block the action of Mpro.

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