Neuropilin 1: A Novel Entry Factor for SARS-CoV-2 Infection and a Potential Therapeutic Target

Abstract

The novel coronavirus disease 2019 (COVID-19) pandemic is severely challenging the healthcare systems and economies of the world, which urgently demand vaccine and therapy development to combat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Hence, advancing our understanding of the comprehensive entry mechanisms of SARS-CoV-2, especially the host factors that facilitate viral infection, is crucial for the discovery of effective vaccines and antiviral drugs. SARS-CoV-2 has previously been documented to reach cells by binding with ACE2 and CD147 receptors in host cells that interact with the spike (S) protein of SARS-CoV-2. A novel entry factor, called neuropilin 1(NRP1), has recently been discovered as a co-receptor facilitating the entry of SARS-CoV-2. NRP1 is a single-pass transmembrane glycoprotein widely distributed throughout the tissues of the body and acts as a multifunctional co-receptor to bind with different ligand proteins and play diverse physiological roles as well as pathological and therapeutic roles in different clinical conditions/diseases, including COVID-19. The current review, therefore, briefly provides the overview of SARS-CoV-2 entry mechanisms, the structure of NRP1, and their roles in health and various diseases, as well as extensively discusses the current understanding of the potential implication of NRP1 in SARS-CoV-2 entry and COVID-19 treatment.

Keywords:

• SARS-COV-2 entry
• neuropilin 1
• COVID-19
• therapeutic target

Abbreviations

ACE2, angiotensin converting enzyme 2; BALF, bronchoalveolar lavage fluid; BMP1, bone morphogenetic protein 1; CendR, C-end rule; COVID-19, coronavirus disease 2019; CUB, complement C1r/C1s, Uegf, BMP1; EGF, epidermal growth factor; FGF-2, fibroblast growth factor 2; HGF, hepatocyte growth factor (HGF); GIPC, RGS-GAIP-interacting protein; Hh-hedgehog; MAM, meprin, A5/NRP1, protein tyrosine phosphatase μ and К; NRP, neuropilin; NRP1, neuropilin 1; NRP2, neuropilin 2; PCOS, polycystic ovarian syndrome; PDGF, platelet-derived growth factor; RRAR, arginine-arginine-alanine-arginine; S protein, spike protein; SARS-CoV, severe acute respiratory syndrome coronavirus; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; SEMA, semaphorin; TGF-β1, transforming growth factor-β1; Uegf, urchin embryonic growth factor; VEGF, vascular endothelial growth factor; VEGFR2, vascular endothelial growth factor receptor 2.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agreed to be accountable for all aspects of the work.

Disclosure

The authors report no conflict of interests for this work.

Additional information

Funding

There is no funding to report.