文章基本信息

标题：Trimeric receptor-binding domain of SARS-CoV-2 acts as a potent inhibitor of ACE2 receptor-mediated viral entry
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作者：Shrikanth C. Basavarajappa ; Angela Rose Liu ; Anna Bruchez 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：8
页码：1-19
DOI：10.1016/j.isci.2022.104716
语种：English
出版社：Elsevier
摘要：SummaryThe COVID-19 pandemic has caused over four million deaths and effective methods to control CoV-2 infection, in addition to vaccines, are needed. The CoV-2 binds to the ACE2 on human cells through the receptor-binding domain (RBD) of the trimeric spike protein. Our modeling studies show that a modified trimeric RBD (tRBD) can interact with three ACE2 receptors, unlike the native spike protein, which binds to only one ACE2. We found that tRBD binds to the ACE2 with 58-fold higher affinity than monomeric RBD (mRBD) and blocks spike-dependent pseudoviral infection over 4-fold more effectively compared to the mRBD. Although mRBD failed to block CoV-2 USA-WA1/2020 infection, tRBD efficiently blocked the true virus infection in plaque assays. We show that tRBD is a potent inhibitor of CoV-2 through both competitive binding to the ACE2 and steric hindrance, and has the potential to emerge as a first-line therapeutic method to control COVID-19.Graphical abstractDisplay OmittedHighlights•tRBD binds multiple ACE2 receptors, while mRBD and spike bind one ACE2 receptor•tRBD shows 4-fold higher inhibition of CoV-2 pseudovirus infection than mRBD•tRBD, yet not mRBD, prevents CoV-2 USA-WA1/2020 from infecting Vero cells•Use of tRBD is a potential therapeutic method to block CoV-2 infectionMolecular structure; Virology.