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

Rory D. de Vries, Katharina S. Schmitz, Francesca T. Bovier, Camilla Predella, Jonathan Khao, Danny Noack, Bart L. Haagmans, Sander Herfst, Kyle N. Stearns, Jennifer Drew-Bear, Sudipta Biswas, Barry Rockx, Gaël McGill, N. Valerio Dorrello, Samuel H. Gellman, Christopher A. Alabi*, Rik L. de Swart, Anne Moscona, Matteo Porotto

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

133 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1379-1382
Number of pages4
Issue number6536
Publication statusPublished - 26 Mar 2021

Bibliographical note

Funding Information:
This work was supported by funding from the National Institutes of Health (AI146980, AI121349, and NS091263 to M.P.; AI114736 to A.M.; and HHSN272201400008C to S.H.), the Sharon Golub Fund at Columbia University Irving Medical Center (CUIMC), the Children's Health Innovation Nucleation Fund of the Pediatrics Department at CUIMC, and a Harrington Discovery Institute COVID-19 Award to A.M. A.M. is the inaugural Sherie L. Morrison Professor of Immunology.

Publisher Copyright: © 2021 American Association for the Advancement of Science. All rights reserved.


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