The oral protease inhibitor (PF-07321332) protects Syrian hamsters against infection with SARS-CoV-2 variants of concern

被引：96

作者：

Abdelnabi, Rana ^{[1
,2
]}

Foo, Caroline S. ^{[1
,2
]}

Jochmans, Dirk ^{[1
,2
]}

Vangeel, Laura ^{[1
,2
]}

De Jonghe, Steven ^{[1
]}

Augustijns, Patrick ^{[3
]}

Mols, Raf ^{[3
]}

Weynand, Birgit ^{[4
]}

Wattanakul, Thanaporn ^{[5
]}

Hoglund, Richard M. ^{[5
,6
]}

Tarning, Joel ^{[5
,6
]}

Mowbray, Charles E. ^{[7
]}

Sjo, Peter ^{[7
]}

Escudie, Fanny ^{[7
]}

Scandale, Ivan ^{[7
]}

Chatelain, Eric ^{[7
]}

Neyts, Johan ^{[1
,2
]}

机构：

[1] Katholieke Univ Leuven, Dept Microbiol Immunol & Transplantat, Rega Inst Med Res, Lab Virol & Chemotherapy, B-3000 Leuven, Belgium

[2] Global Virus Network, Baltimore, MD 21201 USA

[3] Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci Drug Delivery & D, Box 921, B-3000 Leuven, Belgium

[4] Katholieke Univ Leuven, Dept Imaging & Pathol Translat Cell & Tissue Res, B-3000 Leuven, Belgium

[5] Mahidol Univ, Fac Trop Med, Mahidol Oxford Trop Med Res Unit, Bangkok, Thailand

[6] Univ Oxford, Ctr Trop Med & Global Hlth, Nuffield Dept Med, Oxford, England

[7] Drugs Neglected Dis Initiat, Geneva, Switzerland

来源：

NATURE COMMUNICATIONS | 2022年 / 13卷 / 01期

基金：

英国惠康基金; 比尔及梅琳达.盖茨基金会;

关键词：

ANTIVIRAL ACTIVITY;

D O I：

10.1038/s41467-022-28354-0

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

There is an urgent need for potent and selective antivirals against SARS-CoV-2. Pfizer developed PF-07321332 (PF-332), a potent inhibitor of the viral main protease (Mpro, 3CLpro) that can be dosed orally and that is in clinical development. We here report that PF-332 exerts equipotent in vitro activity against the four SARS-CoV-2 variants of concerns (VoC) and that it can completely arrest replication of the alpha variant in primary human airway epithelial cells grown at the air-liquid interface. Treatment of Syrian Golden hamsters with PF-332 (250 mg/kg, twice daily) completely protected the animals against intranasal infection with the beta (B.1.351) and delta (B.1.617.2) SARS-CoV-2 variants. Moreover, treatment of SARS-CoV-2 (B.1.617.2) infected animals with PF-332 completely prevented transmission to untreated co-housed sentinels. There is an urgent need for anti-virals targeting SARS-CoV-2. One of the most promising viral targets is the main protease of SARS-CoV-2, which is essential for viral replication and has no human analogue. Here, Abdelnabi et al. show that one of the most promising anti-virals (PF-07321332), currently in clinical trials, protects against SARS-CoV-2 alpha, beta and delta variant infection and provide evidence of reduced transmission.

引用

页数：9

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