Combination therapy with oral antiviral and anti-inflammatory drugs improves the efficacy of delayed treatment in a COVID-19 hamster model

Sasaki, Michihito; Sugi, Tatsuki; Iida, Shun; Hirata, Yuichiro; Kusakabe, Shinji; Konishi, Kei; Itakura, Yukari; Tabata, Koshiro; Kishimoto, Mai; Kobayashi, Hiroko; Ariizumi, Takuma; Intaruck, Kittiya; Nobori, Haruaki; Toba, Shinsuke; Sato, Akihiko; Matsuno, Keita; Yamagishi, Junya; Suzuki, Tadaki; Hall, William W.; Orba, Yasuko; Sawa, Hirofumi

Combination therapy with oral antiviral and anti-inflammatory drugs improves the efficacy of delayed treatment in a COVID-19 hamster model

Sasaki, Michihito; Sugi, Tatsuki; Iida, Shun et al.

eBioMedicine, 2024, 99, 104950

Permalink : https://hdl.handle.net/2115/91072

このアイテムのアクセス数:649件（2026-01-23 19:50 集計）

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アクセス権	open access
URI	https://hdl.handle.net/2115/91072
タイトル	Combination therapy with oral antiviral and anti-inflammatory drugs improves the efficacy of delayed treatment in a COVID-19 hamster model
著者	Sasaki, Michihito ; Sugi, Tatsuki ; Iida, Shun ; Hirata, Yuichiro ; Kusakabe, Shinji ; Konishi, Kei ; Itakura, Yukari ; Tabata, Koshiro ; Kishimoto, Mai ; Kobayashi, Hiroko ; Ariizumi, Takuma ; Intaruck, Kittiya ; Nobori, Haruaki ; Toba, Shinsuke ; Sato, Akihiko ; Matsuno, Keita ; Yamagishi, Junya ; Suzuki, Tadaki ; Hall, William W. ; Orba, Yasuko ; Sawa, Hirofumi
e-Rad_Researcher 70609403 著者名 Sasaki, Michihito
e-Rad_Researcher 90745944 著者名 Sugi, Tatsuki
e-Rad_Researcher 50785996 著者名 Iida, Shun
e-Rad_Researcher 20896344 著者名 Hirata, Yuichiro
著者名 Kusakabe, Shinji
著者名 Konishi, Kei
e-Rad_Researcher 00980856 著者名 Itakura, Yukari
e-Rad_Researcher 70980837 著者名 Tabata, Koshiro
e-Rad_Researcher 20822068 著者名 Kishimoto, Mai
著者名 Kobayashi, Hiroko
著者名 Ariizumi, Takuma
著者名 Intaruck, Kittiya
著者名 Nobori, Haruaki
著者名 Toba, Shinsuke
著者名 Sato, Akihiko
e-Rad_Researcher 40753306 著者名 Matsuno, Keita
e-Rad_Researcher 80535328 著者名 Yamagishi, Junya
e-Rad_Researcher 30527180 著者名 Suzuki, Tadaki
著者名 Hall, William W.
e-Rad_Researcher 60507169 著者名 Orba, Yasuko
e-Rad_Researcher 30292006 著者名 Sawa, Hirofumi
言語	英語
キーワード	SARS-CoV-2
	COVID-19
	Antiviral therapy
	Corticosteroid
	Hamster
	Delayed treatment
発行日	2024-01
出版者	Elsevier
収録物名	eBioMedicine
巻(号)	99
ページ	104950
抄録	Background Pulmonary infection with SARS-CoV-2 stimulates host immune responses and can also result in the progression of dysregulated and critical inflammation. Throughout the pandemic, the management and treatment of COVID-19 has been continuously updated with a range of antiviral drugs and immunomodulators. Monotherapy with oral antivirals has proven to be effective in the treatment of COVID-19. However, treatment should be initiated in the early stages of infection to ensure beneficial therapeutic outcomes, and there is still room for further consideration on therapeutic strategies using antivirals. Methods We studied the therapeutic effects of monotherapy with the oral antiviral ensitrelvir or the anti-inflammatory corticosteroid methylprednisolone and combination therapy with ensitrelvir and methylprednisolone in a delayed dosing model of hamsters infected with SARS-CoV-2. Findings Combination therapy with ensitrelvir and methylprednisolone improved respiratory conditions and reduced the development of pneumonia in hamsters even when the treatment was started after 2 days post-infection. The combination therapy led to a differential histological and transcriptomic pattern in comparison to either of the monotherapies, with reduced lung damage and down-regulation of expression of genes involved in the inflammatory response. Furthermore, we found that the combination treatment is effective in case of infection with either the highly pathogenic delta or circulating omicron variants. Interpretation Our results demonstrate the advantage of combination therapy with antiviral and corticosteroid drugs in COVID-19 treatment from the perspective of lung pathology and host inflammatory responses.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
権利情報	Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
PISSN	2352-3964
関連情報	PMID 38159532
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.1016/j.ebiom.2023.104950