HUSCAP logo Hokkaido Univ. logo

Hokkaido University Collection of Scholarly and Academic Papers >
International Institute for Zoonosis Control >
Peer-reviewed Journal Articles, etc >

S-217622, a SARS-CoV-2 main protease inhibitor, decreases viral load and ameliorates COVID-19 severity in hamsters

This item is licensed under:Creative Commons Attribution 4.0 International

Files in This Item:
scitranslmed.abq4064.pdf1.89 MBPDFView/Open
Please use this identifier to cite or link to this item:

Title: S-217622, a SARS-CoV-2 main protease inhibitor, decreases viral load and ameliorates COVID-19 severity in hamsters
Authors: Sasaki, Michihito Browse this author →KAKEN DB
Tabata, Koshiro Browse this author
Kishimoto, Mai Browse this author
Itakura, Yukari Browse this author
Kobayashi, Hiroko Browse this author
Ariizumi, Takuma Browse this author
Uemura, Kentaro Browse this author
Toba, Shinsuke Browse this author
Kusakabe, Shinji Browse this author
Maruyama, Yuki Browse this author
Iida, Shun Browse this author →KAKEN DB
Nakajima, Noriko Browse this author →KAKEN DB
Suzuki, Tadaki Browse this author →KAKEN DB
Yoshida, Shinpei Browse this author
Nobori, Haruaki Browse this author
Sanaki, Takao Browse this author
Kato, Teruhisa Browse this author
Shishido, Takao Browse this author
Hall, William W. Browse this author
Orba, Yasuko Browse this author →KAKEN DB
Sato, Akihiko Browse this author
Sawa, Hirofumi Browse this author →KAKEN DB
Issue Date: 18-Jan-2023
Publisher: American Association for the Advancement of Science
Journal Title: Science translational medicine
Volume: 15
Issue: 679
Start Page: eabq4064
Publisher DOI: 10.1126/scitranslmed.abq4064
PMID: 36327352
Abstract: In parallel with vaccination, oral antiviral agents are highly anticipated to act as countermeasures for the treatment of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Oral antiviral medication demands not only high antiviral activity but also target specificity, favorable oral bioavailability, and high metabolic stability. Although a large number of compounds have been identified as potential inhibitors of SARS-CoV-2 infection in vitro, few have proven to be effective in vivo. Here, we show that oral administration of S-217622 (ensitrelvir), an inhibitor of SARS-CoV-2 main protease (Mpro; also known as 3C-like protease), decreases viral load and ameliorates disease severity in SARS-CoV-2-infected hamsters. S-217622 inhibited viral proliferation at low nanomolar to submicromolar concentrations in cells. Oral administration of S-217622 demonstrated favorable pharmacokinetic properties and accelerated recovery from acute SARS-CoV-2 infection in hamster recipients. Moreover, S-217622 exerted antiviral activity against SARS-CoV-2 variants of concern, including the highly pathogenic Delta variant and the recently emerged Omicron BA.5 and BA.2.75 variants. Overall, our study provides evidence that S-217622, an antiviral agent that is under evaluation in a phase 3 clinical trial (clinical trial registration no. jRCT2031210350), has remarkable antiviral potency and efficacy against SARS-CoV-2 and is a prospective oral therapeutic option for COVID-19.
Type: article
Appears in Collections:人獣共通感染症国際共同研究所 (International Institute for Zoonosis Control) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 佐々木 道仁

Export metadata:

OAI-PMH ( junii2 , jpcoar_1.0 )

MathJax is now OFF:


 - Hokkaido University