RT Journal Article SR Electronic T1 Intranasal fusion inhibitory lipopeptide prevents direct contact SARS-CoV-2 transmission in ferrets JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.11.04.361154 DO 10.1101/2020.11.04.361154 A1 Rory D. de Vries A1 Katharina S. Schmitz A1 Francesca T. Bovier A1 Danny Noack A1 Bart L. Haagmans A1 Sudipta Biswas A1 Barry Rockx A1 Samuel H. Gellman A1 Christopher A. Alabi A1 Rik L. de Swart A1 Anne Moscona A1 Matteo Porotto YR 2020 UL http://biorxiv.org/content/early/2020/11/05/2020.11.04.361154.abstract 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.