Neuropilin-1 is a host factor for SARS-CoV-2 infection.
Neuropilin-1 is a host factor for SARS-CoV-2 infection.
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DOI：
10.1126/science.abd3072
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发表时间：
2020-11-13
期刊：
影响因子：
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通讯作者：
Yamauchi Y
中科院分区：
文献类型：
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作者：
Daly JL;Simonetti B;Klein K;Chen KE;Williamson MK;Antón-Plágaro C;Shoemark DK;Simón-Gracia L;Bauer M;Hollandi R;Greber UF;Horvath P;Sessions RB;Helenius A;Hiscox JA;Teesalu T;Matthews DA;Davidson AD;Collins BM;Cullen PJ;Yamauchi Y
SARS-CoV-2是COVID-19的病原体，它使用病毒刺突（S）蛋白来附着和进入宿主细胞。宿主蛋白酶弗林蛋白酶将全长前体S糖蛋白切割成两个相关的多肽：S1和S2。S的切割在S1上产生多碱基Arg-Arg-Ala-Arg C-末端序列，其符合与细胞表面神经纤毛蛋白-1（NRP 1）和神经纤毛蛋白-2（NRP 2）受体结合的C-末端规则（CendR）基序。在这里，使用X射线晶体学和生物化学方法，我们表明，S1 CendR基序直接绑定NRP 1。使用RNAi或选择性抑制剂阻断这种相互作用可降低SARS-CoV-2进入细胞培养物的能力和感染性。因此，NRP 1可作为SARS-CoV-2感染的宿主因子，并可能为COVID-19提供潜在的治疗靶点。
SARS-CoV-2, the causative agent of COVID-19, uses the viral Spike (S) protein for host cell attachment and entry. The host protease furin cleaves the full-length precursor S glycoprotein into two associated polypeptides: S1 and S2. Cleavage of S generates a polybasic Arg-Arg-Ala-Arg C-terminal sequence on S1, which conforms to a C-end rule (CendR) motif that binds to cell surface Neuropilin-1 (NRP1) and Neuropilin-2 (NRP2) receptors. Here, using X-ray crystallography and biochemical approaches we show that the S1 CendR motif directly bound NRP1. Blocking this interaction using RNAi or selective inhibitors reduced SARS-CoV-2 entry and infectivity in cell culture. NRP1 thus serves as a host factor for SARS-CoV-2 infection and may potentially provide a therapeutic target for COVID-19.