Perspectives and potential approaches for targeting neuropilin 1 in SARS-CoV-2 infection

Chapoval, Svetlana P.; Keegan, Achsah

doi:10.1186/s10020-021-00423-y

Cited by 14 publications

(11 citation statements)

References 140 publications

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“…Ackermann et al (2020) showed that the expression of NRP1 was increased in SARS-CoV-2-infected patients [149]; thus, polymorphisms that influence NRP1 expression may play a regulatory role in the further uptake of viral particles. Interestingly, it has been suggested that NRP1 may interact with S1 in the absence of ACE2; however, this requires further investigation [150].…”

Section: Nrp1mentioning

confidence: 96%

Genetic Variants within SARS-CoV-2 Human Receptor Genes May Contribute to Variable Disease Outcomes in Different Ethnicities

Adimulam

Arumugam

Gokul

et al. 2023

IJMS

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The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into a global pandemic, with an alarming infectivity and mortality rate. Studies have examined genetic effects on SARS-CoV-2 disease susceptibility and severity within Eurasian populations. These studies identified contrasting effects on the severity of disease between African populations. Genetic factors can explain some of the diversity observed within SARS-CoV-2 disease susceptibility and severity. Single nucleotide polymorphisms (SNPs) within the SARS-CoV-2 receptor genes have demonstrated detrimental and protective effects across ethnic groups. For example, the TT genotype of rs2285666 (Angiotensin-converting enzyme 2 (ACE2)) is associated with the severity of SARS-CoV-2 disease, which is found at higher frequency within Asian individuals compared to African and European individuals. In this study, we examined four SARS-CoV-2 receptors, ACE2, Transmembrane serine protease 2 (TMPRSS2), Neuropilin-1 (NRP1), and Basigin (CD147). A total of 42 SNPs located within the four receptors were reviewed: ACE2 (12), TMPRSS2 (10), BSG (CD147) (5), and NRP1 (15). These SNPs may be determining factors for the decreased disease severity observed within African individuals. Furthermore, we highlight the absence of genetic studies within the African population and emphasize the importance of further research. This review provides a comprehensive summary of specific variants within the SARS-CoV-2 receptor genes, which can offer a better understanding of the pathology of the SARS-CoV-2 pandemic and identify novel potential therapeutic targets.

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Section: Nrp1mentioning

confidence: 96%

Genetic Variants within SARS-CoV-2 Human Receptor Genes May Contribute to Variable Disease Outcomes in Different Ethnicities

Adimulam

Arumugam

Gokul

et al. 2023

IJMS

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“…A recent study by Zazhytska et al (2022) revealed that SARS‐CoV‐2 can indirectly affect signaling genes without infection, causing COVID‐19‐induced anosmia. Chapoval et al summarized that a pain‐lowering effect caused by interactions between NRP1 and S protein could explain the disease transmission in asymptomatic individuals, compared to the pain‐promoting effect caused by the interaction between S protein and ACE2 (Chapoval and Keegan, 2021). In addition, researchers have hypothesized that one potential pathway to the central nervous system during SARS‐CoV‐2 infection is through the retrograde transport along axons of olfactory sensory neurons, delivering from olfactory epithelium to the olfactory bulb, then toward the olfactory nucleus in the pyriform cortex (Cardona et al, 2020; Davies et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Biophysical investigation of interactions between SARS‐CoV‐2 spike protein and neuropilin‐1

Hou,

Cao,

Kim

et al. 2023

Protein Science

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Recent studies have suggested that neuropilin‐1 (NRP1) may serve as a potential receptor in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) infection. However, the biophysical characteristics of interactions between NRP1 and SARS‐CoV‐2 remain unclear. In this study, we examined the interactions between NRP1 and various SARS‐CoV‐2 spike (S) fragments, including the receptor‐binding domain (RBD) and the S protein trimer in a soluble form or expressed on pseudovirions, using atomic force microscopy (AFM) and structural modeling. Our measurements showed that NRP1 interacts with the RBD and trimer at a higher binding frequency compared to ACE2. This NRP1‐RBD interaction has also been predicted and simulated via AlphaFold2 and molecular dynamic simulations, and the results indicate that their binding patterns are very similar to RBD‐ACE2 interactions. Additionally, under similar loading rates, the most probable unbinding forces between NRP1 and S trimer (both soluble form and on pseudovirions) are larger than the forces between NRP1 and RBD and between trimer and ACE2. Further analysis indicates that NRP1 has a stronger binding affinity to the SARS‐CoV‐2 S trimer with a dissociation rate of 0.87 s‐1, four times lower than the dissociation rate of 3.65 s‐1 between NRP1 and RBD. Moreover, additional experiments show that RBD‐neutralizing antibodies can significantly reduce the binding frequency for both ACE2 and NRP1. Together, the study suggests that NRP1 can be an alternative receptor for SARS‐CoV‐2 attachment to human cells, and the neutralizing antibodies targeting SARS‐CoV‐2 RBD can reduce the binding between SARS‐CoV‐2 and NRP1.This article is protected by copyright. All rights reserved.

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“…Heparan sulfate aids in the attachment of viral particles to the cell surface, while the presence of cleavage sites on the spike protein, which are similar to furin, promote viral replication in the lung [ 23 , 24 ]. Neuropilin1 (NRP1) binds these furin-derived substrates, aiding in the entry of the virus into nasal cells [ 25 , 26 ]. Figure 1 illustrates the mechanism of SARS-CoV-2 maturation into the host cells and its major components.…”

Section: How Does Sars-cov-2 Enter the Host Cells?mentioning

confidence: 99%

Shedding Lights on the Extracellular Vesicles as Functional Mediator and Therapeutic Decoy for COVID-19

Thakur

2023

Life

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COVID-19 is an infectious disease caused by the novel coronavirus (SARS-CoV-2) that first appeared in late 2019 and has since spread across the world. It is characterized by symptoms such as fever, cough, and shortness of breath and can lead to death in severe cases. To help contain the virus, measures such as social distancing, handwashing, and other public health measures have been implemented. Vaccine and drug candidates, such as those developed by Pfizer/BioNTech, AstraZeneca, Moderna, Novavax, and Johnson & Johnson, have been developed and are being distributed worldwide. Clinical trials for drug treatments such as remdesivir, dexamethasone, and monoclonal antibodies are underway and have shown promising results. Recently, exosomes have gained attention as a possible mediator of the COVID-19 infection. Exosomes, small vesicles with a size of around 30–200 nm, released from cells, contain viral particles and other molecules that can activate the immune system and/or facilitate viral entry into target cells. Apparently, the role of exosomes in eliciting various immune responses and causing tissue injury in COVID-19 pathogenesis has been discussed. In addition, the potential of exosomes as theranostic and therapeutic agents for the treatment of COVID-19 has been elaborated.

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Perspectives and potential approaches for targeting neuropilin 1 in SARS-CoV-2 infection

Cited by 14 publications

References 140 publications

Genetic Variants within SARS-CoV-2 Human Receptor Genes May Contribute to Variable Disease Outcomes in Different Ethnicities

Genetic Variants within SARS-CoV-2 Human Receptor Genes May Contribute to Variable Disease Outcomes in Different Ethnicities

Biophysical investigation of interactions between SARS‐CoV‐2 spike protein and neuropilin‐1

Shedding Lights on the Extracellular Vesicles as Functional Mediator and Therapeutic Decoy for COVID-19

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