| 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. |
| Rights: | https://creativecommons.org/licenses/by/4.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/87809 |
| 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)
|
