Prophylactic effect of ensitrelvir in mice infected with SARS-CoV-2.

Autor: Nobori H; Pharmaceutical Research Division, Shionogi & Co., Ltd., 1-1, Futaba-cho 3-chome, Toyonaka, Osaka, 561-0825, Japan. Electronic address: haruaki.nobori@shionogi.co.jp., Baba K; Pharmaceutical Research Division, Shionogi & Co., Ltd., 1-1, Futaba-cho 3-chome, Toyonaka, Osaka, 561-0825, Japan. Electronic address: keiko.baba@shionogi.co.jp., Kuroda T; Pharmaceutical Research Division, Shionogi & Co., Ltd., 1-1, Futaba-cho 3-chome, Toyonaka, Osaka, 561-0825, Japan. Electronic address: takayuki.kuroda@shionogi.co.jp., Baba K; Shionogi TechnoAdvance Research & Co., Ltd., 1-1, Futaba-cho 3-chome, Toyonaka, Osaka, 561-0825, Japan. Electronic address: kaoru.baba@shionogi.co.jp., Matsumoto K; Shionogi TechnoAdvance Research & Co., Ltd., 1-1, Futaba-cho 3-chome, Toyonaka, Osaka, 561-0825, Japan. Electronic address: kazumi.matsumoto@shionogi.co.jp., Yoshida S; Pharmaceutical Research Division, Shionogi & Co., Ltd., 1-1, Futaba-cho 3-chome, Toyonaka, Osaka, 561-0825, Japan. Electronic address: shinpei.yoshida@shionogi.co.jp., Watari R; Pharmaceutical Research Division, Shionogi & Co., Ltd., 1-1, Futaba-cho 3-chome, Toyonaka, Osaka, 561-0825, Japan. Electronic address: ryosuke.watari@shionogi.co.jp., Tachibana Y; Pharmaceutical Research Division, Shionogi & Co., Ltd., 1-1, Futaba-cho 3-chome, Toyonaka, Osaka, 561-0825, Japan. Electronic address: yuki.tachibana@shionogi.co.jp., Kato T; Pharmaceutical Research Division, Shionogi & Co., Ltd., 1-1, Futaba-cho 3-chome, Toyonaka, Osaka, 561-0825, Japan. Electronic address: teruhisa.kato@shionogi.co.jp., Fukao K; Pharmaceutical Research Division, Shionogi & Co., Ltd., 1-1, Futaba-cho 3-chome, Toyonaka, Osaka, 561-0825, Japan. Electronic address: keita.fukao@shionogi.co.jp.
Jazyk: angličtina
Zdroj: Antiviral research [Antiviral Res] 2024 Apr; Vol. 224, pp. 105852. Date of Electronic Publication: 2024 Feb 28.
DOI: 10.1016/j.antiviral.2024.105852
Abstrakt: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological cause of coronavirus disease 2019 (COVID-19) and continues to be a major health concern worldwide. Strategies to protect individuals at high risk of COVID-19 are critical but are currently a largely unmet need. We evaluated the oral antiviral drug ensitrelvir, which specifically targets the SARS-CoV-2 3CL protease, for its efficacy as a pre-exposure prophylactic treatment. Aged BALB/c mice were subcutaneously treated with various doses of ensitrelvir 24 h prior to a lethal SARS-CoV-2 challenge infection. Mouse body weight changes, survival rates, and viral titers in the lungs were evaluated, and plasma concentrations of ensitrelvir were determined. A single subcutaneous administration of ensitrelvir at 64 mg/kg or greater 24 h prior to SARS-CoV-2 challenge infection significantly protected aged mice against lethality and inhibited body weight loss. Pharmacokinetic analysis of ensitrelvir in the aged mice suggested that plasma concentrations ≥2.99 μg/mL resulted in a significant prophylactic effect against SARS-CoV-2 infection. In the aged mouse prophylaxis model, SARS-CoV-2 titers were suppressed in the lungs of mice treated with ensitrelvir 24 h prior to challenge infection, suggesting that the prophylactic administration of ensitrelvir exerted its prophylactic effect by suppressing viral proliferation. These findings suggest that ensitrelvir is a candidate drug for pre-exposure prophylactic treatment of individuals at high risk of COVID-19.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:The authors declare the following competing financial interest(s).
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: