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.

遏制 COVID-19 大流行需要减少病毒传播。严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 感染是由病毒和宿主细胞膜之间的膜融合引发的，该融合由病毒刺突蛋白介导。我们设计了脂肽融合抑制剂来阻断感染的这一关键第一步，并根据体外功效和体内生物分布，选择了一种二聚体形式用于动物模型的评估。在严格的条件下，每天对雪貂进行鼻内给药完全阻止了 SARS-CoV-2 在与受感染动物共居 24 小时期间的直接接触传播，导致 100% 未经治疗的动物被感染。