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

Abebe, Endeshaw Chekol; Ayele, Teklie Mengie; Muche, Zelalem Tilahun; Dejenie, Tadesse Asmamaw

doi:10.2147/btt.s307352

Cited by 32 publications

(27 citation statements)

References 56 publications

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“…Interestingly, one study showed that other newly discovered entry factors for SARS‐CoV‐2 such as NRP1 (Neuropilin 1) 71 , 72 , 73 , 74 and TFRC (Transferrin Receptor) 75 are rather highly co‐expressed with beta cell marker, INSULIN, in healthy pancreata. The study found that while there was no stark difference in ACE2 and TMPRSS2 protein expressions between alpha and beta cells in the islet, both being low, NRP1 and TFRC were selectively expressed in the beta cells with a relatively high expression.…”

Section: Role Of Ace2 In Beta Cell Development Function and Diabetesmentioning

confidence: 99%

ACE2 function in the pancreatic islet: Implications for relationship between SARS‐CoV‐2 and diabetes

Memon

Abdelalim

2021

Acta Physiologica

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The molecular link between SARS‐CoV‐2 infection and susceptibility is not well understood. Nonetheless, a bi‐directional relationship between SARS‐CoV‐2 and diabetes has been proposed. The angiotensin‐converting enzyme 2 (ACE2) is considered as the primary protein facilitating SARS‐CoV and SARS‐CoV‐2 attachment and entry into the host cells. Studies suggested that ACE2 is expressed in the endocrine cells of the pancreas including beta cells, in addition to the lungs and other organs; however, its expression in the islets, particularly beta cells, has been met with some contradiction. Importantly, ACE2 plays a crucial role in glucose homoeostasis and insulin secretion by regulating beta cell physiology. Given the ability of SARS‐CoV‐2 to infect human pluripotent stem cell‐derived pancreatic cells in vitro and the presence of SARS‐CoV‐2 in pancreatic samples from COVID‐19 patients strongly hints that SARS‐CoV‐2 can invade the pancreas and directly cause pancreatic injury and diabetes. However, more studies are required to dissect the underpinning molecular mechanisms triggered in SARS‐CoV‐2‐infected islets that lead to aggravation of diabetes. Regardless, it is important to understand the function of ACE2 in the pancreatic islets to design relevant therapeutic interventions in combatting the effects of SARS‐CoV‐2 on diabetes pathophysiology. Herein, we detail the function of ACE2 in pancreatic beta cells crucial for regulating insulin sensitivity, secretion, and glucose metabolism. Also, we discuss the potential role played by ACE2 in aiding SARS‐COV‐2 entry into the pancreas and the possibility of ACE2 cooperation with alternative entry factors as well as how that may be linked to diabetes pathogenesis.

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Section: Role Of Ace2 In Beta Cell Development Function and Diabetesmentioning

confidence: 99%

ACE2 function in the pancreatic islet: Implications for relationship between SARS‐CoV‐2 and diabetes

Memon

Abdelalim

2021

Acta Physiologica

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“…NRP1 is also used as a surface receptor by different proteins, as the vascular endothelial growth factor (VEGF) or semaphorin 3 family [ 51 ]. NRP1 is expressed in vascular endothelial cells and may contribute to the organ tropism of COVID-19 disease beside the respiratory tract [ 49 , 50 ].…”

Section: General Mechanisms Involving Endocrine Molecules As Sars-cov-2 Viral Targetsmentioning

confidence: 99%

Basic mechanisms of SARS-CoV-2 infection. What endocrine systems could be implicated?

Soldevila

Puig‐Domingo

Marazuela

2021

Rev Endocr Metab Disord

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Although SARS-CoV-2 viral attacks starts by the interaction of spike protein (S Protein) to ACE2 receptor located at the cell surface of respiratory tract and digestive system cells, different endocrine targets, endocrine organs and metabolic conditions are of fundamental relevance for understanding disease progression and special outcomes, in particular those of fatal consequences for the patient. During pandemic, moreover, a specific phenotype of COVID-19 metabolic patient has been described, characterized by being at particular risk of worse outcomes. In the present paper we describe the mechanism of viral interaction with endocrine organs, emphasizing the specific endocrine molecules of particular relevance explaining COVID-19 disease evolution and outcomes.

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“…In contrast, ACE2 causes vasodilation by cleaving and hydrolyzing angiotensin 2 into angiotensin decapeptide 1–7 which signals through the G-protein coupled MasR to induce Akt phosphorylation and NOS production (Bader 2013 ). Structural biology techniques such as Cryo-Electron Microscopy (Cryo-EM) and X-ray crystallography techniques detail the Spike protein interactions with ACE2 guiding the ongoing therapeutic and vaccination efforts (reviewed in Papageorgiou and Mohsin 2020 ; Chekol Abebe et al 2021 ). Rather low to absent ACE2 expression was detected in all compartments of human respiratory tract.…”

Section: Ace2 Structure and Functionmentioning

confidence: 99%

“…These single cell transcriptome data led to several explanations for the observed relatively high human-to-human transmission of SARS-CoV-2 when compared to SARS-CoV or MERS-CoV, namely: (a) the binding of SARSCoV-2 to another, yet unknown receptor on the host cell surface, (b) enhanced cleavage of the SARS-CoV-2 S protein resulting in higher efficiency of the virus’ entry into the cell, and (c) additional host factors increasing the virus entry into the cell by facilitating membrane fusion. All these can explain why SARS-CoV-2 readily infected tissues with relatively low or absent ACE2 expression, such as the respiratory tract and nervous system, pointing to other potentially important factors/receptors for virus entry (reviewed in Chekol Abebe et al 2021 ).…”

Section: Ace2 Structure and Functionmentioning

confidence: 99%

“…Recent studies have shown its expression in dendritic cells, macrophages (alveolar, bronchial, and intravascular; tumor-associated macrophages), T cell subpopulations (CD8+ T cells, Treg cells, Tfh cells, and NKT cells), and mast cells (Bruder et al 2004 ; Chekol Abebe et al 2021 ; Marone et al 2016 ; Roy et al 2017 ; Tordjman et al 2002 ) demonstrating the important role of NRP1 in the regulation of immune response and in respiratory diseases. NRP1 was also found to be expressed on osteoblasts, renal glomerular mesangial cells, glomerular epithelial cells, neuroendocrine cells of the gastrointestinal tract, adipocytes, kidney’s podocytes, olfactory epithelium, and olfactory neurons (reviewed in Chekol Abebe et al 2021 ; Roy et al 2017 ; Ellis 2006 ). Mouse NRP1 is a critical receptor for Sema4A acting on Treg cells to regulate their stability and function (Delgoffe et al 2013 ).…”

Section: Nrp1 Structure and Functionmentioning

confidence: 99%

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

Chapoval

Keegan

2021

Mol Med

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel type b coronavirus responsible for the COVID-19 pandemic. With over 224 million confirmed infections with this virus and more than 4.6 million people dead because of it, it is critically important to define the immunological processes occurring in the human response to this virus and pathogenetic mechanisms of its deadly manifestation. This perspective focuses on the contribution of the recently discovered interaction of SARS-CoV-2 Spike protein with neuropilin 1 (NRP1) receptor, NRP1 as a virus entry receptor for SARS-CoV-2, its role in different physiologic and pathologic conditions, and the potential to target the Spike–NRP1 interaction to combat virus infectivity and severe disease manifestations.

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

Cited by 32 publications

References 56 publications

ACE2 function in the pancreatic islet: Implications for relationship between SARS‐CoV‐2 and diabetes

ACE2 function in the pancreatic islet: Implications for relationship between SARS‐CoV‐2 and diabetes

Basic mechanisms of SARS-CoV-2 infection. What endocrine systems could be implicated?

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

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