Intranasal fusion inhibitory lipopeptide prevents direct-contact SARS-CoV-2 transmission in ferrets

被引：165

作者：

de Vries, Rory D. ^{[1
]}

Schmitz, Katharina S. ^{[1
]}

Bovier, Francesca T. ^{[2
,3
,4
]}

Predella, Camilla ^{[2
,5
]}

Khao, Jonathan ^{[6
]}

Noack, Danny ^{[1
]}

Haagmans, Bart L. ^{[1
]}

Herfst, Sander ^{[1
]}

Stearns, Kyle N. ^{[2
,3
,7
]}

Drew-Bear, Jennifer ^{[2
,3
]}

Biswas, Sudipta ^{[8
]}

Rockx, Barry ^{[1
]}

McGill, Gael ^{[6
,9
]}

Dorrello, N. Valerio ^{[2
]}

Gellman, Samuel H. ^{[10
]}

Alabi, Christopher A. ^{[8
]}

de Swart, Rik L. ^{[1
]}

Moscona, Anne ^{[2
,3
,7
,11
]}

Porotto, Matteo ^{[2
,3
,4
]}

机构：

[1] Erasmus MC, Dept Virosci, Rotterdam, Netherlands

[2] Columbia Univ, Dept Pediat, Vagelos Coll Phys & Surg, New York, NY 10027 USA

[3] Columbia Univ, Ctr Host Pathogen Interact, Vagelos Coll Phys & Surg, New York, NY 10027 USA

[4] Univ Campania Luigi Vanvitelli, Dept Expt Med, Caserta, Italy

[5] Politecn Milan, Dept Biomed Engn, Milan, Italy

[6] Digizyme Inc, Brookline, MA USA

[7] Columbia Univ, Dept Physiol & Cellular Biophys, Vagelos Coll Phys & Surg, New York, NY 10027 USA

[8] Cornell Univ, Robert Frederick Smith Sch Chem & Biomol Engn, Ithaca, NY 14850 USA

[9] Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Ctr Mol & Cellular Dynam, Boston, MA 02115 USA

[10] Univ Wisconsin, Dept Chem, 1101 Univ Ave, Madison, WI 53706 USA

[11] Columbia Univ, Dept Microbiol & Immunol, Vagelos Coll Phys & Surg, New York, NY 10027 USA

来源：

SCIENCE | 2021年 / 371卷 / 6536期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1126/science.abf4896

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：

Containment of the COVID-19 pandemic requires reducing viral transmission. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is initiated by membrane fusion between the viral and host cell membranes, which is mediated by the viral spike protein. We have designed lipopeptide fusion inhibitors that block this critical first step of infection and, on the basis of in vitro efficacy and in vivo biodistribution, selected a dimeric form for evaluation in an animal model. Daily intranasal administration to ferrets completely prevented SARS-CoV- 2 direct-contact transmission during 24-hour cohousing with infected animals, under stringent conditions that resulted in infection of 100% of untreated animals. These lipopeptides are highly stable and thus may readily translate into safe and effective intranasal prophylaxis to reduce transmission of SARS-CoV-2.

引用

页码：1379 / +

页数：27

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