de Vries Rory D, Schmitz Katharina S, Bovier Francesca T, Predella Camilla, Khao Jonathan, Noack Danny, Haagmans Bart L, Herfst Sander, Stearns Kyle N, Drew-Bear Jennifer, Biswas Sudipta, Rockx Barry, McGill Gaël, Dorrello N Valerio, Gellman Samuel H, Alabi Christopher A, de Swart Rik L, Moscona Anne, Porotto Matteo
Department of Viroscience, Erasmus MC, Rotterdam, Netherlands.
Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.
Science. 2021 Mar 26;371(6536):1379-1382. doi: 10.1126/science.abf4896. Epub 2021 Feb 17.
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.
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）感染是由病毒与宿主细胞膜之间的膜融合引发的，这一过程由病毒刺突蛋白介导。我们设计了脂肽融合抑制剂，可阻断这一关键的感染第一步，并根据体外疗效和体内生物分布，选择了一种二聚体形式在动物模型中进行评估。在严格条件下，将感染动物与雪貂共同饲养24小时，此时未治疗的动物100%会被感染，而每天给雪貂鼻腔内给药可完全预防SARS-CoV-2的直接接触传播。这些脂肽高度稳定，因此可能很容易转化为安全有效的鼻腔内预防措施，以减少SARS-CoV-2的传播。
