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

[Snow Leopard]

Neuropilin-1 is a host factor for SARS-CoV-2 infection
James L. Daly, Boris Simonetti, Carlos Antón-Plágaro, Maia Kavanagh Williamson, Deborah K. Shoemark, Lorena Simón-Gracia, Katja Klein, 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, Peter J. Cullen, Yohei Yamauchi

SARS-CoV-2 is the causative agent of COVID-19, a coronavirus disease that has infected more than 6.6 million people and caused over 390,000 deaths worldwide1,2. The Spike (S) protein of the virus forms projections on the virion surface responsible for host cell attachment and penetration. This viral glycoprotein is synthesized as a precursor in infected cells and, to be active, must be cleaved to two associated polypeptides: S1 and S2(3,4). For SARS-CoV-2 the cleavage is catalysed by furin, a host cell protease, which cleaves the S protein precursor at a specific sequence motif that generates a polybasic Arg-Arg-Ala-Arg (RRAR) C-terminal sequence on S1. This sequence motif conforms to the C-end rule (CendR), which means that the C-terminal sequence may allow the protein to associate with cell surface neuropilin-1 (NRP1) and neuropilin-2 (NRP2) receptors5. Here we demonstrate using immunoprecipitation, site-specific mutagenesis, structural modelling, and antibody blockade that, in addition to engaging the known receptor ACE2, S1 can bind to NRP1 through the canonical CendR mechanism. This interaction enhances infection by SARS-CoV-2 in cell culture. NRP1 thus serves as a host factor for SARS-CoV-2 infection, and provides a therapeutic target for COVID-19.

https://www.biorxiv.org/content/10.1101/2020.06.05.134114v1

I must admit I was surprised to see this as I have been recently investigating Neuropilins since they have been shown to be cellular entry receptors for Epstein Barr Virus and Cytomegalovirus in epithelial cells. (anyone thinking "that's interesting" right about now?)

https://www.ncbi.nlm.nih.gov/pubmed/25670642
https://www.ncbi.nlm.nih.gov/pubmed/31439151
https://pubmed.ncbi.nlm.nih.gov/30057110/
See also:
The role of growth factor receptors in viral infections: An opportunity for drug repurposing against emerging viral diseases such as COVID-19?
https://pubmed.ncbi.nlm.nih.gov/32395702/

 

[Snow Leopard]

Part 2:
Integrins are also common viral entry points (including herpesviruses and picornaviruses, Q fever, Ross River virus etc).

SARS‐COV‐2 and infectivity: Possible increase in infectivity associated to integrin motif expression
https://onlinelibrary.wiley.com/doi/10.1002/jmv.25831

A potential role for integrins in host cell entry by SARS-CoV-2
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7114098/

The Integrin Binding Peptide, ATN-161, as a Novel Therapy for SARS-CoV-2 Infection
https://www.biorxiv.org/content/10.1101/2020.06.15.153387v1 (hypothesized α5β1integrin-based mechanism)

An Evolutionary RGD Motif in the Spike Protein of SARS-CoV-2 may Serve as a Potential High Risk Factor for Virus Infection?
https://www.preprints.org/manuscript/202002.0447/v1

Short linear motif candidates in the cell entry system used by SARS-CoV-2 and their potential therapeutic implications
https://arxiv.org/ftp/arxiv/papers/2004/2004.10274.pdf