Naphthalen-1-ylethanamine-containing small molecule inhibitors of the papain-like protease of SARS-CoV-2.

Autor: Shinohara K; Department of Medicinal Chemistry, Laboratory for Biomaterials and Bioengineering, Institute of Integrated Research, Institute of Science Tokyo, Chiyoda-ku, Tokyo, 101-0062, Japan., Kobayakawa T; Department of Medicinal Chemistry, Laboratory for Biomaterials and Bioengineering, Institute of Integrated Research, Institute of Science Tokyo, Chiyoda-ku, Tokyo, 101-0062, Japan., Tsuji K; Department of Medicinal Chemistry, Laboratory for Biomaterials and Bioengineering, Institute of Integrated Research, Institute of Science Tokyo, Chiyoda-ku, Tokyo, 101-0062, Japan., Takamatsu Y; Department of Refractory Viral Infections, National Center for Global Health and Medicine Research Institute, Shinjuku-ku, Tokyo, 162-8655, Japan., Mitsuya H; Department of Refractory Viral Infections, National Center for Global Health and Medicine Research Institute, Shinjuku-ku, Tokyo, 162-8655, Japan; Experimental Retrovirology Section, HIV and AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, United States; Department of Clinical Sciences, Kumamoto University Hospital, Chuo-ku, Kumamoto, 860-8556, Japan., Tamamura H; Department of Medicinal Chemistry, Laboratory for Biomaterials and Bioengineering, Institute of Integrated Research, Institute of Science Tokyo, Chiyoda-ku, Tokyo, 101-0062, Japan. Electronic address: tamamura.mr@tmd.ac.jp.
Jazyk: angličtina
Zdroj: European journal of medicinal chemistry [Eur J Med Chem] 2024 Dec 15; Vol. 280, pp. 116963. Date of Electronic Publication: 2024 Oct 18.
DOI: 10.1016/j.ejmech.2024.116963
Abstrakt: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has not yet been eradicated. SARS-CoV-2 has two types of proteases, a main protease (M pro ) and a papain-like protease (PL pro ), which together process two translated non-structural polyproteins, pp1a and pp1ab, to produce functional viral proteins. In this study, effective inhibitors against PL pro of SARS-CoV-2 were designed and synthesized using GRL-0048 as a lead. A docking simulation of GRL-0048 and SARS-CoV-2 PL pro showed that GRL-0048 noncovalently interacts with PL pro , and there is a newly identified binding pocket in PL pro . Structure-activity relationship studies were next performed on GRL-0048, resulting in the development of several inhibitors, specifically compounds 1, 2b, and 3h, that have more potent inhibitory activity than GRL-0048.
Competing Interests: Declaration of competing interest 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.
(Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
Databáze: MEDLINE
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