Global S&T Development Trend Analysis Platform of Resources and Environment
DOI | 10.1126/science.abd3072 |
Neuropilin-1 is a host factor for SARS-CoV-2 infection | |
James L. Daly; Boris Simonetti; Katja Klein; Kai-En Chen; Maia Kavanagh Williamson; Carlos Antón-Plágaro; Deborah K. Shoemark; Lorena Simón-Gracia; Michael Bauer; Reka Hollandi; Urs F. Greber; Peter Horvath; Richard B. Sessions; Ari Helenius; Julian A. Hiscox; Tambet Teesalu; David A. Matthews; Andrew D. Davidson; Brett M. Collins; Peter J. Cullen; Yohei Yamauchi | |
2020-11-13 | |
发表期刊 | Science
![]() |
出版年 | 2020 |
英文摘要 | Virus-host interactions determine cellular entry and spreading in tissues. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the earlier SARS-CoV use angiotensin-converting enzyme 2 (ACE2) as a receptor; however, their tissue tropism differs, raising the possibility that additional host factors are involved. The spike protein of SARS-CoV-2 contains a cleavage site for the protease furin that is absent from SARS-CoV (see the Perspective by Kielian). Cantuti-Castelvetri et al. now show that neuropilin-1 (NRP1), which is known to bind furin-cleaved substrates, potentiates SARS-CoV-2 infectivity. NRP1 is abundantly expressed in the respiratory and olfactory epithelium, with highest expression in endothelial and epithelial cells. Daly et al. found that the furin-cleaved S1 fragment of the spike protein binds directly to cell surface NRP1 and blocking this interaction with a small-molecule inhibitor or monoclonal antibodies reduced viral infection in cell culture. Understanding the role of NRP1 in SARS-CoV-2 infection may suggest potential targets for future antiviral therapeutics. Science , this issue p. [856][1], p. [861][2]; see also p. [765][3] 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. [1]: /lookup/doi/10.1126/science.abd2985 [2]: /lookup/doi/10.1126/science.abd3072 [3]: /lookup/doi/10.1126/science.abf0732 |
领域 | 气候变化 ; 资源环境 |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/304154 |
专题 | 气候变化 资源环境科学 |
推荐引用方式 GB/T 7714 | James L. Daly,Boris Simonetti,Katja Klein,et al. Neuropilin-1 is a host factor for SARS-CoV-2 infection[J]. Science,2020. |
APA | James L. Daly.,Boris Simonetti.,Katja Klein.,Kai-En Chen.,Maia Kavanagh Williamson.,...&Yohei Yamauchi.(2020).Neuropilin-1 is a host factor for SARS-CoV-2 infection.Science. |
MLA | James L. Daly,et al."Neuropilin-1 is a host factor for SARS-CoV-2 infection".Science (2020). |
条目包含的文件 | 条目无相关文件。 |
除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。
修改评论