Neuropilin-1 is a host factor for SARS-CoV-2 infection

James Daly; Boris Simonetti; Katja Klein; Maia Kavanagh Williamson; Carlos Anton Plagaro; Deborah K Shoemark; Richard B Sessions; David A Matthews; Andrew D Davidson; Pete J Cullen; Yohei Yamauchi

doi:10.1126/science.abd3072

Neuropilin-1 is a host factor for SARS-CoV-2 infection

James Daly, Boris Simonetti^*, Katja Klein, Maia Kavanagh Williamson, Carlos Anton Plagaro, Deborah K Shoemark, Richard B Sessions, David A Matthews, Andrew D Davidson, Pete J Cullen ^*, Yohei Yamauchi^*

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

933 Citations (Scopus)

257 Downloads (Pure)

Abstract

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, we used X-ray crystallography and biochemical approaches to 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.

Original language	English
Article number	eabd3072
Pages (from-to)	861-865
Number of pages	5
Journal	Science
Volume	370
Issue number	6518
Early online date	20 Oct 2020
DOIs	https://doi.org/10.1126/science.abd3072
Publication status	Published - 13 Nov 2020

Research Groups and Themes

BrisSynBio
Covid19
UNCOVER
Bristol BioDesign Institute

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10.1126/science.abd3072

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This is the author accepted manuscript (AAM). The final published version (version of record) is available online via American Association for the Advancement of Science at https://science.sciencemag.org/content/early/2020/10/19/science.abd3072. Please refer to any applicable terms of use of the publisher.
Accepted author manuscript, 7.43 MB

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MRC-AMED - The HDAC6/USP7 axis in enveloped RNA viral infection
Yamauchi, Y. (Principal Investigator)
1/01/20 → 31/12/22
Project: Research
Analysis of flavivirus infection on the cellular lipidome: implications for virus particle production and replication.
Davidson, A. D. (Principal Investigator)
1/04/18 → 31/03/22
Project: Research
Defining the role of retromer-like in endosomal cargo sorting in health and disease
Cullen , P. J. (Principal Investigator)
1/10/17 → 31/03/24
Project: Research

HPC (High Performance Computing) and HTC (High Throughput Computing) Facilities
Alam, S. R. (Manager), Williams, D. A. G. (Manager), Eccleston, P. E. (Manager) & Greene, D. (Manager)
Facility/equipment: Facility

Professor Pete J Cullen
- Pete.Cullenbristol.acuk
- School of Biochemistry - Royal Society Noreen Murray Research Professor
- Dynamic Cell Biology
- Bristol Neuroscience
Person: Academic , Member, Group lead

Cite this

@article{fc897ab34bd74dab85e1f9edae7518f5,

title = "Neuropilin-1 is a host factor for SARS-CoV-2 infection",

abstract = "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, we used X-ray crystallography and biochemical approaches to 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.",

author = "James Daly and Boris Simonetti and Katja Klein and {Kavanagh Williamson}, Maia and {Anton Plagaro}, Carlos and Shoemark, {Deborah K} and Sessions, {Richard B} and Matthews, {David A} and Davidson, {Andrew D} and Cullen, {Pete J} and Yohei Yamauchi",

year = "2020",

month = nov,

day = "13",

doi = "10.1126/science.abd3072",

language = "English",

volume = "370",

pages = "861--865",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

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TY - JOUR

T1 - Neuropilin-1 is a host factor for SARS-CoV-2 infection

AU - Daly, James

AU - Simonetti, Boris

AU - Klein, Katja

AU - Kavanagh Williamson, Maia

AU - Anton Plagaro, Carlos

AU - Shoemark, Deborah K

AU - Sessions, Richard B

AU - Matthews, David A

AU - Davidson, Andrew D

AU - Cullen , Pete J

AU - Yamauchi, Yohei

PY - 2020/11/13

Y1 - 2020/11/13

N2 - 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, we used X-ray crystallography and biochemical approaches to 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.

AB - 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, we used X-ray crystallography and biochemical approaches to 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.

U2 - 10.1126/science.abd3072

DO - 10.1126/science.abd3072

M3 - Article (Academic Journal)

C2 - 33082294

SN - 0036-8075

VL - 370

SP - 861

EP - 865

JO - Science

JF - Science

IS - 6518

M1 - eabd3072

ER -

Neuropilin-1 is a host factor for SARS-CoV-2 infection

Abstract

Research Groups and Themes

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Projects

MRC-AMED - The HDAC6/USP7 axis in enveloped RNA viral infection

Analysis of flavivirus infection on the cellular lipidome: implications for virus particle production and replication.

Defining the role of retromer-like in endosomal cargo sorting in health and disease

Equipment

HPC (High Performance Computing) and HTC (High Throughput Computing) Facilities

Profiles

Professor Pete J Cullen

Cite this