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Comment
. 2021 Jan 18;6(1):21.
doi: 10.1038/s41392-020-00460-9.

Not only ACE2-the quest for additional host cell mediators of SARS-CoV-2 infection: Neuropilin-1 (NRP1) as a novel SARS-CoV-2 host cell entry mediator implicated in COVID-19

Ioannis Kyrou  1   2   3 , Harpal S Randeva  4   5   6 , Demetrios A Spandidos  7 , Emmanouil Karteris  8
Affiliations
Comment

Not only ACE2-the quest for additional host cell mediators of SARS-CoV-2 infection: Neuropilin-1 (NRP1) as a novel SARS-CoV-2 host cell entry mediator implicated in COVID-19

Ioannis Kyrou et al. Signal Transduct Target Ther. .
No abstract available

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
a The SARS-CoV-2 spike (S) glycoproteins facilitate the binding and subsequent fusion of this coronavirus with the host cell membrane. These are cleaved (during the host cell entry or the production of SARS-CoV-2 particles) into two components that remain non-covalently linked, namely S1 which constitutes the cell connecting head of this molecule and S2 which remains anchored to the viral membrane and facilitates its fusion. As such, S1 binds to angiotensin-converting enzyme 2 (ACE2) on the cell membrane, whilst S2 mediates the fusion between the viral and host cell membranes after proteolytic exposure of a S2 fusion peptide by transmembrane protease serine 2 (TMPRSS2) or other host cell proteases, such as furin, located within the host cell secretory pathway and endocytic compartments. Indeed, furin cleaves the SARS-CoV-2 S glycoprotein at the S1-S2 junction/boundary which consists of a sequence of basic amino acids. Notably, this furin-mediated cleavage of the polybasic S1-S2 junction exposes a carboxyl-terminal motif [RRAR, where R represents arginine (Arg): Arg-Arg-Ala-Arg], which conforms to the “C-end rule” (CendR) motif [R-XX-R, where R represents arginine (Arg) and can be substituted by lysine (Lys), whilst X can be any amino acid]. This CendR motif of S1 can bind to neuropilin-1 via its b1 domain (NRP1; a pleiotropic single-transmembrane co-receptor for class-3 semaphorins and vascular endothelial growth factors), which is shown to act as a host cell mediator that can increase the SARS-CoV-2 infectivity and contribute to its tissue/organ tropism.,, b Expression of ACE2 and other cellular mediators (e.g., TMPRSS2, and NRP1) that facilitate the infection of host cells by SARS-CoV-2 has been noted in various tissues/organs of the human body and may contribute to the tropism of SARS-CoV-2 and corresponding COVID-19 manifestations.– c Co-expression of ACE2, TMPRSS2, and NRP1 that mediate the SARS-CoV-2 infection of host cells in various human tissues/organs, based on available data from the Genotype-Tissue Expression (GTEx) project
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Comment on

  • Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity.
    Cantuti-Castelvetri L, Ojha R, Pedro LD, Djannatian M, Franz J, Kuivanen S, van der Meer F, Kallio K, Kaya T, Anastasina M, Smura T, Levanov L, Szirovicza L, Tobi A, Kallio-Kokko H, Österlund P, Joensuu M, Meunier FA, Butcher SJ, Winkler MS, Mollenhauer B, Helenius A, Gokce O, Teesalu T, Hepojoki J, Vapalahti O, Stadelmann C, Balistreri G, Simons M. Cantuti-Castelvetri L, et al. Science. 2020 Nov 13;370(6518):856-860. doi: 10.1126/science.abd2985. Epub 2020 Oct 20. Science. 2020. PMID: 33082293 Free PMC article.
  • Neuropilin-1 is a host factor for SARS-CoV-2 infection.
    Daly JL, Simonetti B, Klein K, Chen KE, Williamson MK, Antón-Plágaro C, Shoemark DK, Simón-Gracia L, Bauer M, Hollandi R, Greber UF, Horvath P, Sessions RB, Helenius A, Hiscox JA, Teesalu T, Matthews DA, Davidson AD, Collins BM, Cullen PJ, Yamauchi Y. Daly JL, et al. Science. 2020 Nov 13;370(6518):861-865. doi: 10.1126/science.abd3072. Epub 2020 Oct 20. Science. 2020. PMID: 33082294 Free PMC article.

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