de Vries Rory D, Schmitz Katharina S, Bovier Francesca T, Noack Danny, Haagmans Bart L, Biswas Sudipta, Rockx Barry, Gellman Samuel H, Alabi Christopher A, de Swart Rik L, Moscona Anne, Porotto Matteo
Department Viroscience, Erasmus MC, Rotterdam, the Netherlands.
Department of Pediatrics, Columbia University Medical Center, New York, NY, USA.
bioRxiv. 2020 Nov 5:2020.11.04.361154. doi: 10.1101/2020.11.04.361154.
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 and transmission .
控制新冠疫情需要减少病毒传播。严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染是由病毒刺突蛋白介导的病毒与宿主细胞膜之间的膜融合引发的。我们设计了一种二聚体脂肽融合抑制剂,可阻断新兴冠状病毒感染的这一关键第一步,并证明它能完全预防雪貂感染SARS-CoV-2。每天对雪貂进行鼻内给药,在导致100%未治疗动物感染的严格条件下,与感染动物共同饲养24小时期间,完全预防了SARS-CoV-2的直接接触传播。这些脂肽高度稳定且无毒,因此很容易转化为一种安全有效的鼻内预防方法,以减少SARS-CoV-2的传播。
源自SARS-CoV-2的脂肽的二聚体形式是融合、感染和传播的有效抑制剂。