Emerging Role of Neuropilin-1 and Angiotensin-Converting Enzyme-2 in Renal Carcinoma-Associated COVID-19 Pathogenesis

Hossain, Md. Golzar; Akter, Sharmin; Uddin, Jamal

doi:10.3390/idr13040081

Cited by 6 publications

(3 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…NRP1 expression is upregulated in many cancer types, including kidney renal clear cell carcinoma (KIRC) and kidney renal papillary cell carcinoma (KIRP), compared to the matched healthy tissues and is positively correlated with the survivability rate of KIRC patients [71]. The high-affinity binding between the SARS-CoV-2 S-protein and NRP1 suggested that this binding might play a role in COVID-19 severity since their binding promotes SARS-CoV-2 invasion through NRP1.…”

Section: Discussionmentioning

confidence: 99%

Natural Product Cordycepin (CD) Inhibition for NRP1/CD304 Expression and Possibly SARS-CoV-2 Susceptibility Prevention on Cancers

Li,

Luo,

et al. 2023

Microorganisms

View full text Add to dashboard Cite

NRP1/CD304 is a typical membrane-bound co-receptor for the vascular endothelial cell growth factor (VEGF), semaphorin family members, and viral SARS-CoV-2. Cordycepin (CD) is a natural product or active gradient from traditional Chinese medicine (TCM) from Cordyceps militaris Link and Ophiocordyceps sinensis (Berk.). However, NRP1 expression regulation via CD in cancers and the potential roles and mechanisms of SARS-CoV-2 infection are not clear. In this study, online databases were analyzed, Western blotting and quantitative RT-PCR were used for NRP1 expression change via CD, molecular docking was used for NRP/CD interaction, and a syncytial formation assay was used for CD inhibition using a pseudovirus SARS-CoV-2 entry. As a result, we revealed that CD inhibits NRP1 expressed in cancer cells and prevents viral syncytial formation in 293T-hACE2 cells, implying the therapeutic potential for both anti-cancer and anti-viruses, including anti-SARS-CoV-2. We further found significant associations between NRP1 expressions and the tumor–immune response in immune lymphocytes, chemokines, receptors, immunostimulators, immune inhibitors, and major histocompatibility complexes in most cancer types, implying NRP1’s roles in both anti-cancer and anti-SARS-CoV-2 entry likely via immunotherapy. Importantly, CD also downregulated the expression of NRP1 from lymphocytes in mice and downregulated the expression of A2AR from the lung cancer cell line H1975 when treated with CD, implying the NRP1 mechanism probably through immuno-response pathways. Thus, CD may be a therapeutic component for anti-cancer and anti-viral diseases, including COVID-19, by targeting NRP1 at least.

show abstract

Section: Discussionmentioning

confidence: 99%

Natural Product Cordycepin (CD) Inhibition for NRP1/CD304 Expression and Possibly SARS-CoV-2 Susceptibility Prevention on Cancers

Li,

Luo,

et al. 2023

Microorganisms

View full text Add to dashboard Cite

show abstract

“…Direct viral action refers to the active uptake of SARS-CoV-2 into ECs through binding with the angiotensin-converting enzyme 2 receptor (ACE 2) and co-receptors: transmembrane serine protease 2 (TMPRSS2), cathepsin L1 (CTSL) or neuropilin 1 (NRP1) [43] , [44] . ACE2 is the cell receptor responsible for SARS-CoV-2 entry, with binding affinity being 10 to 20-fold higher when compared with SARS-CoV-1 binding to ACE2 [45] .…”

Section: Covid-19 Disease and The Endotheliummentioning

confidence: 99%

The role of the endothelium in severe acute respiratory syndrome coronavirus 2 infection and pathogenesis

Passi

Brittan

2023

Current Opinion in Physiology

View full text Add to dashboard Cite

“…Then again, the viral antigens interact with the host’s immune cells, and this interaction initiates pro-inflammatory reactions such as vasodilation, increased capillary permeability, and the gathering of humoral factors [ 14 ]. Both NRP-1 and ACE2 are expressed in the kidney and are linked to various renal diseases [ 15 ]. All of these factors cause the impedance of gas exchange and dyspnea.…”

Section: Introductionmentioning

confidence: 99%

Correlations between Kidney and Heart Function Bioindicators and the Expressions of Toll-Like, ACE2, and NRP-1 Receptors in COVID-19

et al. 2022

View full text Add to dashboard Cite

Background: COVID-19 impacts the cardiovascular system resulting in myocardial damage, and also affects the kidneys leading to renal dysfunction. This effect is mostly through the binding with angiotensin-converting enzyme 2 (ACE2) and Neuropilin-1 (NRP-l) receptors. Toll-Like Receptors (TLRs) typically combine with microbial pathogens and provoke an inflammatory response. Aim: This work aims to compare the changes in kidney and heart function bioindicators and expressions of TLRs (TLR2 and TLR2) as well as ACE2 and NRP-l receptors in moderate and severe COVID-19 patients. The correlations between kidney and heart function bioindicators and expressions of these receptors are also studied. Patients and Methods: In this study, 50 healthy control and 100 COVID-19 patients (55 males and 45 females) were enrolled. According to WHO guidelines, these participants were divided into severe (50 cases) and moderate (50 cases). Serum creatinine, blood urea, CK-MB, LDH, and Troponin I were estimated. We measured the gene expression for Toll-Like Receptors (TLR2 and TLR4), ACE2, and NRP-1 in the blood samples using quantitative real-time PCR (qRT-PCR). Results: In comparison with the healthy group, all patients exhibited a significant elevation in serum creatinine, urea, cardiac enzymes (CK-MB and LDH), and CRP. Serum Troponin I level was significantly increased in severe COVID-19 patients. Furthermore, all studied patients revealed a significant elevation in the expression levels of TLR2, TLR4, ACE2, and NRP-1 mRNA. In all patients, CK-MB, ACE2, and NRP-1 mRNA expression levels were positively correlated with both TLR2 and TLR4 expression levels. Moreover, serum creatinine and urea levels were positively correlated with both TLR2 and TLR 4 expression levels in the severe group only. In the moderate group, serum CK-MB activity and Troponin I level had a significant positive correlation with both NRP-1 and ACE2 expression levels, while serum urea level and LDH activity had a significant positive correlation with NRP-1 only. In severe patients, the increases in serum creatinine, urea, CK-MB, and LDH were significantly associated with the elevations in both ACE2 and NRP-1 expression levels, whereas serum Troponin I level had a positive direct relationship with NRP-1 only. Conclusions: Our study concluded that expression levels for TLR2, TLR4, ACE2, and NRP-1 mRNA in both severe and moderate patients were positively correlated with renal biomarkers and cardiac enzymes. Innate immune markers can be important because they correlate with the severity of illness in COVID-19.

show abstract

Emerging Role of Neuropilin-1 and Angiotensin-Converting Enzyme-2 in Renal Carcinoma-Associated COVID-19 Pathogenesis

Cited by 6 publications

References 38 publications

Natural Product Cordycepin (CD) Inhibition for NRP1/CD304 Expression and Possibly SARS-CoV-2 Susceptibility Prevention on Cancers

Natural Product Cordycepin (CD) Inhibition for NRP1/CD304 Expression and Possibly SARS-CoV-2 Susceptibility Prevention on Cancers

The role of the endothelium in severe acute respiratory syndrome coronavirus 2 infection and pathogenesis

Correlations between Kidney and Heart Function Bioindicators and the Expressions of Toll-Like, ACE2, and NRP-1 Receptors in COVID-19

Contact Info

Product

Resources

About