2025-10-03 東京科学大学
図1. SARS-CoV-2の複製サイクルとパパイン様プロテアーゼ阻害剤9r
<関連情報>
- https://www.isct.ac.jp/ja/news/qg0ja5jmxcwb
- https://www.isct.ac.jp/plugins/cms/component_download_file.php?type=2&pageId=&contentsId=1&contentsDataId=2387&prevId=&key=b3bf3653728d170d8510811cf734ed36.pdf
- https://pubs.acs.org/doi/10.1021/acsomega.5c05856
ナフタレン-1-イルエタナミンとハロゲン化ベンゼン部位に基づくSARS-CoV-2パパイン様プロテアーゼ阻害剤 SARS-CoV-2 Papain-Like Protease Inhibitors Based on Naphthalen-1-ylethanamine and Halogenated Benzene Moieties
Kouki Shinohara,Takuya Kobayakawa,Kohei Tsuji,Yuki Takamatsu,Hiroaki Mitsuya,and Hirokazu Tamamura
ACS Omega Published: October 2, 2025
DOI:https://doi.org/10.1021/acsomega.5c05856
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the causative virus of COVID-19, remains a worldwide health threat. SARS-CoV-2 possesses two types of proteases: a main protease (Mpro, 3C-like) and a papain-like protease (PLpro). These proteases cleave two translated nonstructural proteins, pp1a and pp1ab, into viral functional proteins. In the present study, we developed new inhibitors targeting the PLpro of SARS-CoV-2 based on GRL-0048 (2) as a lead compound. Structure–activity relationship (SAR) researches on GRL-0048 (2) led to the finding of compound 9r, which showed significantly enhanced inhibitory activity against PLpro. This enhancement was accomplished by the introduction of a halogenated aromatic carbonyl moiety into the parent structure of GRL-0048 (2).
