Neuropilins: C-end rule peptides and their association with nociception and COVID-19

Jobe, Amie; Vijayan, Ranjit

doi:10.1016/j.csbj.2021.03.025

Cited by 19 publications

(21 citation statements)

References 33 publications

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“…Indeed, through its exposed C-end rule (CendR) motif following the furin processing, the SARS-CoV-2 spike protein binds to the NRP1 CendR pocket, which allows it to achieve endocytosis and cell entry. This binding interferes with that of NRP1's endogenous ligand VEGF-A, a signaling that would otherwise promote nociception [21]. The ensuing silencing of pain through the VEGF-A pathway may underlie increased disease transmission in asymptomatic individuals [22].…”

Section: The Less Well-known Nrp-1 Role and Its Remarkable Potentialmentioning

confidence: 99%

“…Hence, this NRP1 binding could stimulate the separation of S1 and S2 domains, which will probably increase the infectivity of SARS-CoV-2 as the liberated S2 mediates the fusion of the virus and other host membranes [23]. As such, NRP1 may increase viral infection by SARS-CoV-2 in the presence of other host factors like ACE2 [21], and it may also initiate receptor-dependent viral internalization, potentiate severe immune-pathological inflammation, and lead to a systemic spread of the infection [8], independently of ACE2. Nonetheless, recent in-vitro studies are showing that NRP1 alone did not increase cell susceptibility to viral infectivity [24], suggesting that it may enhance viral infectivity via other host factors, rather than mediate it itself.…”

Section: The Less Well-known Nrp-1 Role and Its Remarkable Potentialmentioning

confidence: 99%

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Diabetic Nephropathy and COVID-19: The Potential Role of Immune Actors

Mourad

Azar

2021

IJMS

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Nowadays, type II diabetes mellitus, more specifically ensuing diabetic nephropathy, and severe COVID-19 disease are known to be closely associated. The exact mechanisms behind this association are less known. An implication for the angiotensin-converting enzyme 2 remains controversial. Some researchers have started looking into other potential actors, such as neuropilin-1, mitochondrial glutathione, vitamin D, and DPP4. In particular, neuropilin-1 seems to play an important role in the underlying mechanism linking COVID-19 and diabetic nephropathy. We suggest, based on the findings in this review, that its up-regulation in the diabetic kidney facilitates viral entry in this tissue, and that the engagement of both processes leads to a depletion of neuropilin-1, which was demonstrated to be strongly associated with the pathogenesis of DN. More studies are needed to confirm this hypothesis, and research should be directed towards elucidating the potential roles of all these suggested actors and eventually discovering new therapeutic strategies that could reduce the burden of COVID-19 in patients with diabetic nephropathy.

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Section: The Less Well-known Nrp-1 Role and Its Remarkable Potentialmentioning

confidence: 99%

Section: The Less Well-known Nrp-1 Role and Its Remarkable Potentialmentioning

confidence: 99%

Diabetic Nephropathy and COVID-19: The Potential Role of Immune Actors

Mourad

Azar

2021

IJMS

View full text Add to dashboard Cite

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“…NRP-1 is implicated in several aspects of a SARS-CoV-2 infection, including possible spread through the olfactory bulb and into the central nervous system and increased NRP-1 RNA expression in lungs of severe COVID-19 [54]. Moreover, NRP-1 may also serve as an immune checkpoint of the memory T cell in COVID-19 [55]. It has been identified that binding of the SARS-CoV-2 spike protein to the NRP-1 receptors impacts the docking of the VEGF-A ligand [55].…”

Section: Sites Of Sars-cov-2 Invasionmentioning

confidence: 99%

“…Moreover, NRP-1 may also serve as an immune checkpoint of the memory T cell in COVID-19 [55]. It has been identified that binding of the SARS-CoV-2 spike protein to the NRP-1 receptors impacts the docking of the VEGF-A ligand [55]. NRP-1 may act as a host cell mediator that is able to increase the infectivity of the virus and thus contribute to the tropism of the coronavirus [56].…”

Section: Sites Of Sars-cov-2 Invasionmentioning

confidence: 99%

Pathophysiology and Clinical Manifestations of COVID-19-Related Acute Kidney Injury—The Current State of Knowledge and Future Perspectives

Smarz-Widelska¹,

Grywalska

Morawska

et al. 2021

IJMS

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The continually evolving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has resulted in a vast number of either acute or chronic medical impairments of a pathophysiology that is not yet fully understood. SARS-CoV-2 tropism for the organs is associated with bilateral organ cross-talks as well as targeted dysfunctions, among which acute kidney injury (AKI) seems to be highly prevalent in infected patients. The need for efficient management of COVID-related AKI patients is an aspect that is still being investigated by nephrologists; however, another reason for concern is a disturbingly high proportion of various types of kidney dysfunctions in patients who have recovered from COVID-19. Even though the clinical picture of AKI and COVID-related AKI seems to be quite similar, it must be considered that regarding the latter, little is known about both the optimal management and long-term consequences. These discrepancies raise an urgent need for further research aimed at evaluating the molecular mechanisms associated with SARS-CoV-2-induced kidney damage as well as standardized management of COVID-related AKI patients. The following review presents a comprehensive and most-recent insight into the pathophysiology, clinical manifestations, recommended patient management, treatment strategies, and post-mortem findings in patients with COVID-related AKI.

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“…NRP-1 is a membrane-bound co-receptor to a tyrosine kinase receptor for both vascular endothelial growth factor and semaphorin family members. Recently, NRP-1 has been identified as a possible novel factor for SARS-CoV-2 host cell entry [103]. After cleaving by furin, S1 and S2 proteins are exposed.…”

Section: Neuropilin-1mentioning

confidence: 99%

The Fight against COVID-19 on the Multi-Protease Front and Surroundings: Could an Early Therapeutic Approach with Repositioning Drugs Prevent the Disease Severity?

et al. 2021

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The interaction between the membrane spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the transmembrane angiotensin-converting enzyme 2 (ACE2) receptor of the human epithelial host cell is the first step of infection, which has a critical role for viral pathogenesis of the current coronavirus disease-2019 (COVID-19) pandemic. Following the binding between S1 subunit and ACE2 receptor, different serine proteases, including TMPRSS2 and furin, trigger and participate in the fusion of the viral envelope with the host cell membrane. On the basis of the high virulence and pathogenicity of SARS-CoV-2, other receptors have been found involved for viral binding and invasiveness of host cells. This review comprehensively discusses the mechanisms underlying the binding of SARS-CoV2 to ACE2 and putative alternative receptors, and the role of potential co-receptors and proteases in the early stages of SARS-CoV-2 infection. Given the short therapeutic time window within which to act to avoid the devastating evolution of the disease, we focused on potential therapeutic treatments—selected mainly among repurposing drugs—able to counteract the invasive front of proteases and mild inflammatory conditions, in order to prevent severe infection. Using existing approved drugs has the advantage of rapidly proceeding to clinical trials, low cost and, consequently, immediate and worldwide availability.

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Neuropilins: C-end rule peptides and their association with nociception and COVID-19

Abstract: Graphical abstract Binding of the SARS-CoV-2 S1 CendR peptide to neuropilin-1 aids host invasion, while the binding of the VEGF-A 164 CendR peptide is associated with nociception.

Cited by 19 publications

References 33 publications

Diabetic Nephropathy and COVID-19: The Potential Role of Immune Actors

Diabetic Nephropathy and COVID-19: The Potential Role of Immune Actors

Pathophysiology and Clinical Manifestations of COVID-19-Related Acute Kidney Injury—The Current State of Knowledge and Future Perspectives

The Fight against COVID-19 on the Multi-Protease Front and Surroundings: Could an Early Therapeutic Approach with Repositioning Drugs Prevent the Disease Severity?

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