ArticleBiophysical journal2021
Neuropilin-1 assists SARS-CoV-2 infection by stimulating the separation of Spike protein S1 and S2.
Article in Biophysical journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Smoking and vaping alter genes related to mechanisms of SARS-CoV-2 susceptibility and severity: a systematic review and meta-analysis.The European respiratory journal · 2024Pooled it
- HLA-C-derived peptide MH-1 as an early-stage intervention against SARS-CoV-2 infection.Molecular medicine (Cambridge, Mass.) · 2026Article
- Placental infection by SARS-CoV-2: exploring alternative entry pathways.Tissue barriers · 2026Article
- Pharmacoinformatics-based screening and construction of a neutralizing anti-SARS-CoV-2 camelidae nanobody drug conjugate.Molecular diversity · 2025Article
- Molecular mechanisms of SARS-CoV-2 entry: implications for biomedical strategies.Microbiology and molecular biology reviews : MMBR · 2025Review
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- Hypoxia signaling in cancer: HIF-1α stimulated by COVID-19 can lead to cancer progression and chemo-resistance in oral squamous cell carcinoma (OSCC).Discover oncology · 2025Review
- iPSC-derived human cortical organoids display profound alterations of cellular homeostasis following SARS-CoV-2 infection and Spike protein exposure.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
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- Comprehensive Risk Assessment of Infection Induced by SARS-CoV-2.Molecular neurobiology · 2024Review
- miR-24-3p Is Antiviral Against SARS-CoV-2 by Downregulating Critical Host Entry Factors.Viruses · 2024Article
- Receptors Involved in COVID-19-Related Anosmia: An Update on the Pathophysiology and the Mechanistic Aspects.International journal of molecular sciences · 2024Review
- Potential Effects of Hyperglycemia on SARS-CoV-2 Entry Mechanisms in Pancreatic Beta Cells.Viruses · 2024Review
- SLC38A9 regulates SARS-CoV-2 viral entry.iScience · 2024Article
- NRP1 is a receptor for mammalian orthoreovirus engaged by distinct capsid subunits.Cell host & microbe · 2024Article
- Precision nutrition to reset virus-induced human metabolic reprogramming and dysregulation (HMRD) in long-COVID.NPJ science of food · 2024Review
- Flow cytometry for extracellular vesicle characterization in COVID-19 and post-acute sequelae of SARS-CoV-2 infection.Extracellular vesicles and circulating nucleic acids · 2024Review
- Biophysical investigation of interactions between SARS-CoV-2 spike protein and neuropilin-1.Protein science : a publication of the Protein Society · 2023Article
- Out of the ESCPE room: Emerging roles of endosomal SNX-BARs in receptor transport and host-pathogen interaction.Traffic (Copenhagen, Denmark) · 2023Review
- Mutating novel interaction sites in NRP1 reduces SARS-CoV-2 spike protein internalization.iScience · 2023Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The cell surface receptor Neuropilin-1 (Nrp1) was recently identified as a host factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry. The Spike protein of SARS-CoV-2 is cleaved into two segments, the S1 (residues (res.) 1-685) and the S2 (res. 686-1273) domains by furin protease. Nrp1 predominantly binds to the C-terminal RRAR amino acid motif (res. 682-685) of the S1 domain. In this study, we firstly modeled the association of an Nrp1 protein (consisting of domains a2-b1-b2) with the Spike protein. Next, we studied the separation of S2 from the S1 domain, with and without Nrp1 bound, by utilizing molecular dynamics pulling simulations. During the separation, Nrp1 stabilizes the S1 C-terminal region (res. 640-685) and thereby assists the detachment of S2 N-terminal region (res. 686-700). Without Nrp1 bound, S1 tends to become stretched, whereas the bound Nrp1 stimulates an earlier separation of S2 from the S1 domain. The liberated S2 domain is known to mediate the fusion of virus and host membranes; thus, Nrp1 likely increases virus infectivity by facilitating the S1 and S2 separation. We further analyzed the possible topological structure of the SARS-CoV-2 Spike protein when bound with Nrp1 and angiotensin-converting enzyme 2 (ACE2). Understanding of such an Nrp1-assisted viral infection opens the gate for the generation of protein-protein inhibitors, such as antibodies, which could attenuate the infection mechanism and protect certain cells in a future Nrp1-ACE2 targeted combination therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.