期刊
SCIENCE
卷 370, 期 6518, 页码 861-+出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.abd3072
关键词
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资金
- Wellcome Trust from the Dynamic Molecular Cell Biology Ph.D. program [203959/Z/16/Z]
- Beca Fundacion Ramon Areces Estudios Postdoctorales en el Extranjero
- MRC [MR/P018807/1, MR/R020566/1]
- Wellcome Trust [104568/Z/14/2]
- Lister Institute of Preventive Medicine
- European Research Council under the European Union's Horizon 2020 research and innovation program [856581 - CHUbVi]
- MRC-AMED [MR/T028769/1]
- Swiss National Science Foundation
- Kanton Zurich
- Australian National Health and Medical Research Council (NHMRC) [APP1136021, APP1156493]
- United States Food and Drug Administration [HHSF223201510104C]
- Elizabeth Blackwell Institute for Health Research Rapid Response Call (COVID-19)
- LENDULET-BIOMAG Grant [2018-342]
- H2020discovAIR [874656]
- Chan Zuckerberg Initiative, Seed Networks for the HCA-DVP
- European Regional Development Fund [2014-2020.4.01.15-0012]
- European Research Council grant GLIOGUIDE
- Estonian Research Council [PRG230, EAG79]
- BBSRC [BB/L01386X/1, BB/M02542X/1] Funding Source: UKRI
- MRC [MR/R020566/1, MR/P018807/1, MR/T028769/1, MR/V027506/1] Funding Source: UKRI
- Wellcome Trust [203959/Z/16/Z] Funding Source: Wellcome Trust
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (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 carboxyl-terminal sequence on S1, which conforms to a C-end rule (CendR) motif that binds to cell surface neuropilin-1 (NRP1) and NRP2 receptors. We used x-ray crystallography and biochemical approaches to show that the S1 CendR motif directly bound NRP1. Blocking this interaction by RNA interference 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.
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