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
Affiliations
Fatema Tuz Zohora
Department of Pharmaceutical Chemistry, University of Dhaka, Dhaka 1000, Bangladesh
A. T. M. Zafrul Azam
Department of Pharmaceutical Chemistry, University of Dhaka, Dhaka 1000, Bangladesh
Sinthyia Ahmed
Division of Computer Aided Drug Design, The Red-Green Research Centre, BICCB, Tejgaon, Dhaka 1219, Bangladesh
Khondaker Miraz Rahman
School of Cancer and Pharmaceutical Science, King’s College London, 150 Stamford Street, London SE1 9NH, UK
Mohammad A. Halim
Department of Chemistry and Biochemistry, Kennesaw State University, Kennesaw, GA 30144, USA
Md. Rafi Anwar
College of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71201, USA
Md. Hossain Sohrab
Bangladesh Council of Scientific and Industrial Research (BCSIR), Dr. Qudrat-E-Khuda Road, Dhaka 1205, Bangladesh
Fatema Tabassum
Department of Pharmaceutical Chemistry, University of Dhaka, Dhaka 1000, Bangladesh
Choudhury Mahmood Hasan
Department of Pharmaceutical Chemistry, University of Dhaka, Dhaka 1000, Bangladesh
Monira Ahsan
Department of Pharmaceutical Chemistry, University of Dhaka, Dhaka 1000, Bangladesh
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.
