tetano
Editor, Senior Moderator
Antiviral Res
. 2024 Feb 28:105852.
doi: 10.1016/j.antiviral.2024.105852. Online ahead of print. Prophylactic effect of ensitrelvir in mice infected with SARS-CoV-2
Haruaki Nobori[SUP] 1 [/SUP], Keiko Baba[SUP] 2 [/SUP], Takayuki Kuroda[SUP] 3 [/SUP], Kaoru Baba[SUP] 4 [/SUP], Kazumi Matsumoto[SUP] 5 [/SUP], Shinpei Yoshida[SUP] 6 [/SUP], Ryosuke Watari[SUP] 7 [/SUP], Yuki Tachibana[SUP] 8 [/SUP], Teruhisa Kato[SUP] 9 [/SUP], Keita Fukao[SUP] 10 [/SUP]
Affiliations
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.
Keywords: Antiviral; COVID-19; Ensitrelvir; Pre-exposure prophylactic treatment; Protease inhibitor; SARS-CoV-2.
. 2024 Feb 28:105852.
doi: 10.1016/j.antiviral.2024.105852. Online ahead of print. Prophylactic effect of ensitrelvir in mice infected with SARS-CoV-2
Haruaki Nobori[SUP] 1 [/SUP], Keiko Baba[SUP] 2 [/SUP], Takayuki Kuroda[SUP] 3 [/SUP], Kaoru Baba[SUP] 4 [/SUP], Kazumi Matsumoto[SUP] 5 [/SUP], Shinpei Yoshida[SUP] 6 [/SUP], Ryosuke Watari[SUP] 7 [/SUP], Yuki Tachibana[SUP] 8 [/SUP], Teruhisa Kato[SUP] 9 [/SUP], Keita Fukao[SUP] 10 [/SUP]
Affiliations
- PMID: 38428748
- DOI: 10.1016/j.antiviral.2024.105852
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.
Keywords: Antiviral; COVID-19; Ensitrelvir; Pre-exposure prophylactic treatment; Protease inhibitor; SARS-CoV-2.