new binding target for SARS-CoV-2

Exciting new breakthrough in our understanding? These articles might be of interest to some of you.

SARS-CoV-2 binds not only to ACE, but also to neuropilin receptor-1.
—DwN

In silico identification and validation of inhibitors of the interaction between neuropilin receptor 1 and SARS-CoV-2 Spike protein.

Perez-Miller S, Patek M, Moutal A, Cabel CR, Thorne CA, Campos SK, Khanna R.bioRxiv. 2020 Sep 23:2020.09.22.308783. doi: 10.1101/2020.09.22.308783. Preprint.PMID: 32995772 Free PMC article.

Neuropilin‑1 as a new potential SARS‑CoV‑2 infection mediator implicated in the neurologic features and central nervous system involvement of COVID‑19.

Davies J, Randeva HS, Chatha K, Hall M, Spandidos DA, Karteris E, Kyrou I.Mol Med Rep. 2020 Nov;22(5):4221-4226. doi: 10.3892/mmr.2020.11510. Epub 2020 Sep 15.PMID: 33000221 Free PMC article.

COMMENT:
Thanks, Dan. Here is another paper on NRP1: https://www.biorxiv.org/content/10.1101/2020.06.07.137802v3, whose summary states—

The causative agent of the current pandemic and coronavirus disease 2019 (COVID-19) is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Understanding how SARS-CoV-2 enters and spreads within human organs is crucial for developing strategies to prevent viral dissemination. For many viruses, tissue tropism is determined by the availability of virus receptors on the surface of host cells. Both SARS-CoV and SARS-CoV-2 use angiotensin-converting enzyme 2 (ACE2) as a host receptor, yet, their tropisms differ. Here, we found that the cellular receptor neuropilin-1 (NRP1), known to bind furin-cleaved substrates, significantly potentiates SARS-CoV-2 infectivity, which was inhibited by a monoclonal blocking antibody against the extracellular b1b2 domain of NRP1. NRP1 is abundantly expressed in the respiratory and olfactory epithelium, with highest expression in endothelial cells and in the epithelial cells facing the nasal cavity. Neuropathological analysis of human COVID-19 autopsies revealed SARS-CoV-2 infected NRP1-positive cells in the olfactory epithelium and bulb. In the olfactory bulb, infection was detected particularly within NRP1-positive endothelial cells of small capillaries and medium-sized vessels. Studies in mice demonstrated, after intranasal application, NRP1-mediated transport of virus-sized particles into the central nervous system. Thus, NRP1 could explain the enhanced tropism and spreading of SARS-CoV-2.

Mutated SARS-CoV-2, however, does not appear even to need NRP1. Oh my! ☹

And this publication came out yesterday in Science from the same research group:

Cantuti-Castelvetri L (and 28 additional authors). Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity. Science 20 Oct 2020; eabd2985. doi: 10.1126/science.abd2985. Epub ahead of print. PMID: 33082293.

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