文章基本信息

标题：Artesunate induces substantial topological alterations in the SARS-CoV-2 Nsp1 protein structure
本地全文：下载
作者：Arun Bahadur Gurung ; Arun Bahadur Gurung ; Mohammad Ajmal Ali 等
期刊名称：Journal of King Saud University - Science
印刷版ISSN：1018-3647
出版年度：2022
卷号：34
期号：2
页码：1-9
DOI：10.1016/j.jksus.2021.101810
语种：English
出版社：Elsevier
摘要：AbstractThe need for novel antiviral treatments for coronavirus disease 2019 (COVID-19) continues with the widespread infections and fatalities throughout the world. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the deadly disease, relies on the non-structural protein Nsp1 for multiplication within the host cells and disarms the host immune defences by various mechanisms. Herein, we investigated the potential of artemisinin and its derivatives as possible inhibitors of SARS-CoV-2 Nsp1 through various computational approaches. Molecular docking results show that artemisinin (CID68827) binds to Nsp1 with a binding energy of −6.53 kcal/mol and an inhibition constant of 16.43 µM. The top 3 derivatives Artesunate (CID6917864), Artemiside (CID53323323) and Artemisone (CID11531457) show binding energies of −7.92 kcal/mol, −7.46 kcal/mol and −7.36 kcal/mol respectively. Hydrophobic interactions and hydrogen bonding with Val10, Arg11, and Gln50 helped to stabilize the protein–ligand complexes. The pharmacokinetic properties of these molecules show acceptable properties. The geometric parameters derived from large-scale MD simulation studies provided insights into the changes in the structural topology of Nsp1 upon binding of Artesunate. Thus, the findings of our research highlight the importance of artemisinin and its derivatives in the development of drugs to inhibit SARS-CoV-2 Nsp1 protein.
关键词：Artemisinin;Artemisinin derivatives;Artesunate;COVID-19;Nsp1;SARS-CoV-2