Abstract
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 Statement
RDdV, FTB, RLdS, AM and MP are listed as inventors on a provisional patent application covering findings reported in this manuscript.
Footnotes
Contacts details: - Christopher A. Alabi: caa238{at}cornell.edu - Rik L. de Swart: r.deswart{at}erasmusmc.nl - Anne Moscona: am939{at}cumc.columbia.edu - Matteo Porotto: mp3509{at}cumc.columbia.edu
