PT  - JOURNAL ARTICLE
AU  - Rory D. de Vries
AU  - Katharina S. Schmitz
AU  - Francesca T. Bovier
AU  - Danny Noack
AU  - Bart L. Haagmans
AU  - Sudipta Biswas
AU  - Barry Rockx
AU  - Samuel H. Gellman
AU  - Christopher A. Alabi
AU  - Rik L. de Swart
AU  - Anne Moscona
AU  - Matteo Porotto
TI  - Intranasal fusion inhibitory lipopeptide prevents direct contact SARS-CoV-2 transmission in ferrets
AID  - 10.1101/2020.11.04.361154
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.11.04.361154
4099  - http://biorxiv.org/content/early/2020/11/05/2020.11.04.361154.short
4100  - http://biorxiv.org/content/early/2020/11/05/2020.11.04.361154.full
AB  - Containment of the COVID-19 pandemic requires reducing viral transmission. SARS-CoV-2 infection is initiated by membrane fusion between the viral and host cell membranes, mediated by the viral spike protein. We have designed a dimeric lipopeptide fusion inhibitor that blocks this critical first step of infection for emerging coronaviruses and document that it completely prevents SARS-CoV-2 infection in ferrets. Daily intranasal administration to ferrets completely prevented SARS-CoV-2 direct-contact transmission during 24-hour co-housing with infected animals, under stringent conditions that resulted in infection of 100% of untreated animals. These lipopeptides are highly stable and non-toxic and thus readily translate into a safe and effective intranasal prophylactic approach to reduce transmission of SARS-CoV-2.One-sentence summary A dimeric form of a SARS-CoV-2-derived lipopeptide is a potent inhibitor of fusion and infection in vitro and transmission in vivo.Competing Interest StatementRDdV, FTB, RLdS, AM and MP are listed as inventors on a provisional patent application covering findings reported in this manuscript.