Human Coronavirus Cell Receptors Provide Challenging Therapeutic Targets

López-Cortés, Georgina I.; Palacios-Pérez, Miryam; Hernández-Aguilar, Margarita M.; Veledíaz, Hannya F.; José, Marco V.

doi:10.3390/vaccines11010174

Cited by 5 publications

(7 citation statements)

References 165 publications

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“…The Omicron and its subvariant BA.4/BA.5 have a lower hydrophobic potential compare to most of the other previously identified variants. Omicron’s RBD including the Omicron subvariant BA.4/BA.5 consists of a positive electrostatic surface, while the ACE2 receptor contains many negatively charged residues; therefore, strong binding due to coulombic interactions at the protein-protein interface region is possible [32]. Moreover, since these positively charged RBD mutations exist within the antibody neutralization epitope regions, they could serve to facilitate immune escape.…”

Section: Resultsmentioning

confidence: 99%

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Molecular Investigations of Selected Spike Protein Mutations in SARS-CoV-2: Delta and Omicron Variants and Omicron Subvariants

Roy

2022

Preprint

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Among the multiple SARS-CoV-2 variants recently reported, the delta variant has generated most perilous and widespread effects. Another variant, omicron, has been identified specifically for its high transmissibility. Omicron contains numerous spike (S) protein mutations and in numbers much larger than those of its predecessor variants. BA.2, a sub variant of omicron, has recently emerged with more spreadable infectivity as compared to the original omicron species. BA.2 also contains several new and additional mutations in its spike protein, and represents the globally most prevalent form of SARS-CoV-2 at the present time.In this report we discuss some essential structural aspects and time-based structure changes of a selected set of spike protein mutations within the delta and omicron variants, including those of omicron BA.2. The expected impact of multiple-point mutations within the spike protein’s receptor-binding domain (RBD) and S1 are also discussed. It is expected that the structural data discussed in this report will be helpful to identify drug targets and to neutralize antibodies for the evolving variants/sub variants of SARS-CoV-2.

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Section: Resultsmentioning

confidence: 99%

“…Glycosylation sites are important as they play critical roles in immune evasion. Since BF.7 has mutation R346T close to N331 and N343 (two N-linked glycosylation sites of S1 RBD), that could possibly be linked to higher immune escape [32,39].…”

Section: Resultsmentioning

confidence: 99%

Molecular Investigations of Selected Spike Protein Mutations in SARS-CoV-2: Delta and Omicron Variants and Omicron Subvariants

Roy

2022

Preprint

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“…Recent studies have indicated that ANPEP , which codes for CD13, may also play a role in the viral entry process. In certain cell types, ANPEP can function as an alternative or co-receptor for the virus [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Pathobiological alterations affecting the distinct clinical courses of pediatric versus adult COVID-19 syndrome

ŞENEL,

TÜRK,

MALKAN

et al. 2023

Turkish Journal of Medical Sciences

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Background/aim The clinical presentation of pediatric coronavirus disease 2019 (COVID-19) is associated with a milder disease course than the adult COVID-19 syndrome. The disease course of COVID-19 has three clinicobiological phases: initiation, propagation, and complication. This study aimed to assess the pathobiological alterations affecting the distinct clinical courses of COVID-19 in pediatric age groups versus the adult population. We hypothesized that critical biogenomic marker expressions drive the mild clinical presentations of pediatric COVID-19. Materials and methods Blood samples were obtained from 72 patients with COVID-19 hospitalized at Ankara City Hospital between March and July 2021. Peripheral blood mononuclear cells were isolated using Ficoll-Paque and density-gradient sedimentation. The groups were compared using a t-test and limma analyses. Mean standardized gene expression levels were used to hierarchically cluster genes employing Euclidean Gene Cluster 3.0. The expression levels of identified genes were determined using reverse transcription-polymerase chain reaction. Results This study found that ANPEP gene expression was significantly downregulated in the pediatric group (p < 0.05, FC: 1.57) and IGF2R gene expression was significantly upregulated in the adult group (p < 0.05, FC: 2.98). The study results indicated that the expression of critical biogenomic markers, such as the first-phase ( ACE2 and ANPEP ) and second-phase ( EGFR and IGF2R ) receptor genes, was crucial in the genesis of mild clinical presentations of pediatric COVID-19. ANPEP gene expression was lower in pediatric COVID-19. Conclusion The interrelationship between the ANPEP and ACE2 genes may prevent the progression of COVID-19 from initiation to the propagating phase in pediatric patients. High IGF2R gene expression could potentially contribute to a protective effect and may be a contributing factor for the mild clinical course observed in pediatric patients.

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“…DPP-4, through its intracellular tail, transmits signals by cleaving proline, alanine and glycine [ 15 ]. N-terminal sialylation of membrane-bound DPP-4 increases its apical secretion, and thus may promote virus interaction [ 16 ], as is demonstrated in the case of MERS-CoV, where DPP-4 interacts with the N-glycan-containing receptor-binding domain (RBD) of the virus [ 17 , 18 ]. The membrane-bound form of DPP-4 is ubiquitous, present in T lymphocytes, monocytes, hepatocytes, kidney, lung, small intestine, pancreas, spleen and the heart [ 14 , 19 , 20 ].…”

Section: Dpp-4 and Its Implications In Covid-19mentioning

confidence: 99%

DPP-4 Inhibitors as a Savior for COVID-19 Patients with Diabetes

et al. 2023

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Diabetic patients are at particular risk of severe COVID-19. Human dipeptidyl peptidase-4 (DPP-4) is a membrane-bound aminopeptidase that regulates insulin release by inactivating incretin. DPP-4 inhibitors (DPP-4is) are therefore used as oral anti-diabetic drugs to restore normal insulin levels. These molecules also have anti-inflammatory and anti-hypertension effects. Recent studies on the interactions of SARS-CoV-2 spike glycoprotein and DPP-4 predict a possible entry route for SARS-CoV-2. Therefore, DPP-4is could be effective at reducing the virus-induced ‘cytokine storm’, thereby ceasing inflammatory injury to vital organs. Moreover, DPP-4is may interfere with viral entry into host cells. Herein, we have reviewed the efficacy of DPP-4is as potential repurposed drugs to reduce the severity of SARS-CoV-2 infection in patients with diabetes.

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Human Coronavirus Cell Receptors Provide Challenging Therapeutic Targets

Cited by 5 publications

References 165 publications

Molecular Investigations of Selected Spike Protein Mutations in SARS-CoV-2: Delta and Omicron Variants and Omicron Subvariants

Molecular Investigations of Selected Spike Protein Mutations in SARS-CoV-2: Delta and Omicron Variants and Omicron Subvariants

Pathobiological alterations affecting the distinct clinical courses of pediatric versus adult COVID-19 syndrome

DPP-4 Inhibitors as a Savior for COVID-19 Patients with Diabetes

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