Structure-based virtual screening and molecular dynamics simulation studies to discover new SARS-CoV-2 main protease inhibitors.

Autor: Ibezim A; Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka, Nigeria., Onuku RS; Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka, Nigeria., Ibezim A; Information and Communication Technology Unit, University of Nigeria, Nsukka, Nigeria., Ntie-Kang F; Department of Chemistry, Faculty of Science, University of Buea, P. O. Box 63, Buea, Cameroon.; Institute for Pharmacy, Martin-Luther-Universität Halle-Wittenberg, Kurt-Mothes-Str. 3, 06120 Halle (Saale), Germany.; Institute of Botany, Technical University of Dresden, Zellescher Weg 20b, 01217 Dresden, Germany., Nwodo NJ; Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka, Nigeria., Adikwu MU; Department of Pharmaceutical Microbiology and Biopharmaceutics, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka, Nigeria.
Jazyk: angličtina
Zdroj: Scientific African [Sci Afr] 2021 Nov; Vol. 14, pp. e00970. Date of Electronic Publication: 2021 Sep 14.
DOI: 10.1016/j.sciaf.2021.e00970
Abstrakt: Computational methods were used to filter two datasets (> 8,000 compounds) based on two criteria: higher binding affinity for M PRO than cocrystallized inhibitor and binding interactions with M PRO catalytic dyad (Cys145 and His41). After virtual screening involving ranking and reranking, eleven compounds were identified to satisfy these criteria and analysis of their structures revealed an unparallel common features among them which could be critical for their interactions with M PRO . However, only the topmost scoring compound (AV-203: K i  = 0.31 µM) exhibited relatively stable binding interaction during the period of 50 ns MD simulation and thus is a suitable template for drug development.
Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(© 2021 Published by Elsevier B.V. on behalf of African Institute of Mathematical Sciences / Next Einstein Initiative.)
Databáze: MEDLINE
Externí odkaz: