Daly, James L, Simonetti, Boris, Klein, Katja, Chen, Kai-En, Williamson, Maia Kavanagh, Anton-Plagaro, Carlos, Shoemark, Deborah K, Simon-Gracia, Lorena, Bauer, Michael, Hollandi, Reka et al (show 11 more authors)
(2020)
Neuropilin-1 is a host factor for SARS-CoV-2 infection.
SCIENCE, 370 (6518).
861-+.
Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Caco-2 Cells, Hela Cells, Humans, Pneumonia, Viral, Coronavirus Infections, Furin, Peptidyl-Dipeptidase A, Peptide Fragments, Neuropilin-1, Antibodies, Monoclonal, Crystallography, X-Ray, Mutagenesis, Site-Directed, RNA Interference, Amino Acid Motifs, Protein Binding, Virus Internalization, Protein Interaction Domains and Motifs, Pandemics, Spike Glycoprotein, Coronavirus, Betacoronavirus, COVID-19, Angiotensin-Converting Enzyme 2, SARS-CoV-2 |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 16 Nov 2020 10:13 |
| Last Modified: | 18 Jan 2023 23:21 |
| DOI: | 10.1126/science.abd3072 |
| Open Access URL: | https://science.sciencemag.org/content/370/6518/86... |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3106865 |
Dimensions
Dimensions
