Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity

doi:10.1126/science.abd2985

GSTDTAP > 气候变化

DOI	10.1126/science.abd2985
	Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity
	Ludovico Cantuti-Castelvetri; Ravi Ojha; Liliana D. Pedro; Minou Djannatian; Jonas Franz; Suvi Kuivanen; Franziska van der Meer; Katri Kallio; Tuğberk Kaya; Maria Anastasina; Teemu Smura; Lev Levanov; Leonora Szirovicza; Allan Tobi; Hannimari Kallio-Kokko; Pamela Österlund; Merja Joensuu; Frédéric A. Meunier; Sarah J. Butcher; Martin Sebastian Winkler; Brit Mollenhauer; Ari Helenius; Ozgun Gokce; Tambet Teesalu; Jussi Hepojoki; Olli Vapalahti; Christine Stadelmann; Giuseppe Balistreri; Mikael Simons
	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] The causative agent of coronavirus disease 2019 (COVID-19) is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For many viruses, tissue tropism is determined by the availability of virus receptors and entry cofactors on the surface of host cells. In this study, we found that neuropilin-1 (NRP1), known to bind furin-cleaved substrates, significantly potentiates SARS-CoV-2 infectivity, an effect blocked by a monoclonal blocking antibody against NRP1. A SARS-CoV-2 mutant with an altered furin cleavage site did not depend on NRP1 for infectivity. Pathological analysis of olfactory epithelium obtained from human COVID-19 autopsies revealed that SARS-CoV-2 infected NRP1-positive cells facing the nasal cavity. Our data provide insight into SARS-CoV-2 cell infectivity and define a potential target for antiviral intervention. [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/304153
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Ludovico Cantuti-Castelvetri,Ravi Ojha,Liliana D. Pedro,et al. Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity[J]. Science,2020.
APA	Ludovico Cantuti-Castelvetri.,Ravi Ojha.,Liliana D. Pedro.,Minou Djannatian.,Jonas Franz.,...&Mikael Simons.(2020).Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity.Science.
MLA	Ludovico Cantuti-Castelvetri,et al."Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity".Science (2020).