Structural and non-structural proteins in SARS-CoV-2: potential aspects to COVID-19 treatment or prevention of progression of related diseases

Cell Communication and Signaling, Год журнала: 2023, Номер 21(1)

Опубликована: Май 15, 2023

Coronavirus disease 2019 (COVID-19) is caused by a new member of the Coronaviridae family known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There are structural and non-structural proteins (NSPs) in genome this virus. S, M, H, E proteins, NSPs include accessory replicase proteins. The NSP components SARS-CoV-2 play an important role its infectivity, some them may be pathogenesis chronic diseases, including cancer, coagulation disorders, neurodegenerative cardiovascular diseases. interact with targets such angiotensin-converting enzyme (ACE2) receptor. In addition, can stimulate pathological intracellular signaling pathways triggering transcription factor hypoxia-inducible factor-1 (HIF-1), neuropilin-1 (NRP-1), CD147, Eph receptors, which roles progression diseases like Alzheimer's disease, epilepsy, multiple sclerosis, cancers glioblastoma, lung malignancies, leukemias. Several compounds polyphenols, doxazosin, baricitinib, ruxolitinib could inhibit these interactions. It has been demonstrated that spike protein stronger affinity for human ACE2 than SARS-CoV, leading current study to hypothesize newly produced variant Omicron receptor-binding domain (RBD) binds more strongly primary strain. SARS Middle East (MERS) viruses against have become resistant previous vaccines. Therefore, review recent studies performance vaccines their effects on COVID-19 related vital need deal conditions. This examines potential initiation it anticipated serve effective vaccine or treatment Video Abstract.

Язык: Английский

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Serum biomarkers of inflammation and vascular damage upon SARS-Cov-2 mRNA vaccine in patients with thymic epithelial tumors

Clinical Chemistry and Laboratory Medicine (CCLM), Год журнала: 2024, Номер 62(6), С. 1198 - 1205

Опубликована: Янв. 17, 2024

Abstract Objectives Thymic epithelial tumors (TET) patients are at high risk of autoimmune and hypoimmune complications. Limited evidence is available on the potential immune-related inflammatory reactions induced by SARS-Cov-2 vaccine in this patient population. Methods In order to identify subjects higher for complications, we prospectively evaluated a panel serum biomarkers related inflammation (TNF-α, IL-1β, −6, −10, −12, −17A, IFN-α, β γ, MPO, MMP-9), vascular damage (E- P-selectin, VEGF-A, P-ANCA MCP-1) 44 TET 30 healthy controls along whole cycle. Results About 50 % (either controls) showed an increase biochemical markers endothelial with large heterogeneity values. Such appeared early, after first dose control later, second (in which observed mainly biomarkers). The values normalized about 3 months did not third, booster dose. No or complications were study no difference was terms response among showing those who experienced changes. Conclusions Our data highlight relevance Sars-Cov-2 patients, as it resulted safe prevented severe COVID-19. However, further studies awaited explore mechanisms consequences biomarkers.

Язык: Английский

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Neurological sequelae of long COVID: a comprehensive review of diagnostic imaging, underlying mechanisms, and potential therapeutics

Frontiers in Neurology, Год журнала: 2025, Номер 15

Опубликована: Фев. 7, 2025

One lingering effect of the COVID-19 pandemic created by SARS-CoV-2 is emergence Long COVID (LC), characterized enduring neurological sequelae affecting a significant portion survivors. This review provides thorough analysis these disruptions with respect to cognitive dysfunction, which broadly manifest as chronic insomnia, fatigue, mood dysregulation, and impairments dysfunction. Furthermore, we characterize how diagnostic tools such PET, MRI, EEG, ultrasonography provide critical insight into subtle anomalies that may mechanistically explain disease phenotype. In this review, explore mechanistic hypotheses changes, describe CNS invasion, neuroinflammation, blood-brain barrier disruption, gut-brain axis along novel vascular disruption hypothesis highlights endothelial dysfunction hypoperfusion core underlying mechanism. We lastly evaluate clinical treatment landscape, scrutinizing efficacy various therapeutic strategies ranging from antivirals anti-inflammatory agents in mitigating multifaceted symptoms LC.

Язык: Английский

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Vascular endothelial growth factor A: friend or foe in the pathogenesis of HIV and SARS-CoV-2 infections?

Frontiers in Cellular and Infection Microbiology, Год журнала: 2025, Номер 14

Опубликована: Фев. 11, 2025

This review article discusses the role of vascular endothelial growth factor A (VEGF-A) in pathogenesis SARS-CoV-2 and HIV infection, both conditions being renowned for their impact on endothelium. The processes involved homeostasis angiogenesis are reviewed briefly before exploring interplay between hypoxia, VEGF-A, neuropilin-1 (NRP-1), inflammatory pathways. We then focus infection show how binding viral pathogen to angiotensin-converting enzyme 2 receptor, as well NRP-1, leads elevated levels VEGF-A consequences such coagulation, dysfunction, inflammation. augments via several mechanisms, most prominently, by trans-activator transcription ( tat ) protein mimicking its VEGFR-2, upregulation which enhances interaction VEGFR-2. propose that observed during HIV/SARS-CoV-2 co-infection originate predominantly from activated immune cells due HIF-1α damaged cells. In this context, a few clinical trials have described diminished requirement oxygen therapy anti-VEGF treatment infection. currently available strategies target VEGFR-1 blocking receptors could, however, lead negative outcome, inhibiting not only pathological, but also physiological angiogenesis. Based examination published studies, suggests targeting selective inhibition may be beneficial context

Язык: Английский

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VEGF-A in COVID-19: a systematic review and meta-analytical approach to its prognostic value

Clinical and Experimental Medicine, Год журнала: 2025, Номер 25(1)

Опубликована: Март 12, 2025

Abstract Numerous studies have reported vascular endothelial growth factor A (VEGF-A) has a significant impact on the pathophysiology of COVID-19. The objective this systematic review and meta-analysis is to determine prognostic value increased levels VEGF-A in individuals with literature search was conducted across multiple electronic databases, including PubMed, Web Science, Cochrane Library, Scopus, EMBASE, Google Scholar, up January 2024. Studies examining serum or plasma COVID-19 patients were incorporated, specific attention given contrasting severe/critical cases against moderate cases. Standardized mean differences (SMD) 95% confidence intervals (CIs) calculated using random-effects model overall effect sizes. Meta-regressions subgroup analyses performed explore potential sources heterogeneity. synthesized data from 11 involving total 1119 patients. Elevated significantly associated disease severity, pooled SMD 0.525 (95% CI 0.239–0.058; P = 0.028). Research indicated that nature relationship differs among various age groups, there minor discrepancies techniques employed obtain measurements. Furthermore, meta-regression analysis correlation between assay technique body mass index (BMI). This provides compelling evidence for potency Understanding intricate interplay holds promise development targeted therapeutic strategies indicators management

Язык: Английский

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Profile of synovial inflammatory mediators in patients with knee osteoarthritis following SARS-CoV-2 infection

Minerva Biotechnology and Biomolecular Research, Год журнала: 2025, Номер 37(1)

Опубликована: Март 1, 2025

Язык: Английский

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Altered Circulating Cytokine Profile Among mRNA‐Vaccinated Young Adults: A Year‐Long Follow‐Up Study

Immunity Inflammation and Disease, Год журнала: 2025, Номер 13(4)

Опубликована: Апрель 1, 2025

ABSTRACT Objectives This longitudinal study aimed to assess the impact of COVID‐19 vaccination on cytokine profile. Methods A total 84 Saudi subjects (57.1% females) with mean age 27.2 ± 12.3 participated in this study. Anthropometric data and fasting blood samples were obtained at baseline after final vaccination, an average follow‐up duration 14.1 3.6 months for adolescents 13.3 3.0 adults, calculated from first dose vaccination. Assessment profiles was done using commercially available assays. Results After follow‐up, a significant increase weight body mass index observed overall ( p = 0.003 0.002, respectively). Postvaccination, increases several cytokines, including basic fibroblast growth factor 2 < 0.001), interferon gamma (IFNγ) 0.005), interleukin‐1 beta (IL1β) IL4 IL6 0.003), IL7 IL17E monocyte chemoattractant protein‐1 (MCP1) 0.03), MCP3 tumor necrosis alpha (TNFα) VEGFA 0.001). reduction only macrophage colony‐stimulating When adjusted age, epidermal (EGF), IL4, IL6, MCP3, TNFα, vascular endothelial (VEGFA) remained statistically significant. Gender‐based analysis revealed that men experienced greater 0.008), 0.04), TNFα 0.015) compared women. Age‐based showed older participants had more pronounced EGF 0.011), 0.029), MCP1 0.042), 0.017), while younger 0.025). Conclusions The findings indicated resulted levels, which signifies persistence humoral immune response messenger RNA (mRNA) vaccines. effect may be attributed persistent production spike protein highly inflammatory nature mRNA–lipid nanoparticle. Additionally, results suggested differences levels based gender age. Notably, profile remains favorably altered young adults who received mRNA vaccinations, even 1 year.

Язык: Английский

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The levels of inflammatory, angiogenic, and stress biomarkers in plasma of donors depending on anti-SARS-CoV-2 IgG titers

INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine), Год журнала: 2025, Номер 21(2), С. 112 - 120

Опубликована: Апрель 1, 2025

Background. Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has led to widespread illness and global health challenges. While phase of infection been extensively studied, long-term effects, particularly in individuals who have recovered, remain unclear. Post-acute complications SARS-CoV-2 involves prolonged symptoms systemic disorders, including persistent inflammation, endothelial dysfunction, immune dysregulation, which often last for months. Among key factors contributing these conditions, there are pro-inflammatory cytokines, growth involved angiogenesis, hypoxia-inducible stress-related proteins, play a significant role tissue repair response modulation. The research aimed evaluate degree determine levels pro-angiogenic factors, сellular hypoxia marker HIF-1α, heat shock such as HSP60 HSP70, plasma healthy donors recovered from COVID-19, with particular focus on relationship between biomarkers anti-SARS-CoV-2 IgG titers. Materials methods. This ages 25 45 years, had COVID-19 at least 3 6 months prior beginning study. All patients were divided into groups based their inflammatory TNF-α, transcription factor NF-κB, angiogenic VEGF, PDGF FGF-2, hypoxic proteins measured enzyme-linked immunosorbent assay. Group differences analyzed using ANOVA Tukey’s test or Kruskal-Wallis Dunn’s test, presenting results median interquartile range, significance p ≤ 0.05. Results. study found parameters among donor varying There was an increase markers, TNF-α higher PDGF, FGF-2 showed distinct patterns, VEGF generally reduced, except group titers 95 ± 5 125 10 Index (S/C), where they significantly increased. notably 175 (S/C). HIF-1α also increased 75 (S/C) compared those without IgG. In contrast, HSP70 reduced all reference group, could indicate possible abnormalities mechanisms stress after COVID-19. Conclusions. Our suggest that activation, angiogenesis-related pathways crucial pathogenesis post-COVID-19 complications, underscoring need therapeutic strategies address chronic impaired recovery.

Язык: Английский

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Vascular Pathogenesis in Acute and Long COVID: Current Insights and Therapeutic Outlook

Seminars in Thrombosis and Hemostasis, Год журнала: 2024, Номер unknown

Опубликована: Сен. 30, 2024

Abstract Long coronavirus disease 2019 (COVID-19)—a postacute consequence of severe acute respiratory syndrome 2 infection—manifests with a broad spectrum relapsing and remitting or persistent symptoms as well varied levels organ damage, which may be asymptomatic present events such heart attacks strokes recurrent infections, hinting at complex underlying pathogenic mechanisms. Central to these is vascular dysfunction rooted in thrombotic endothelialitis. We review the scientific evidence that widespread endothelial (ED) leads chronic symptomatology. briefly examine molecular pathways contributing pathology provide detailed analysis how cellular processes underpin clinical picture. Noninvasive diagnostic techniques, flow-mediated dilation peripheral arterial tonometry, are evaluated for their utility identifying ED. then explore mechanistic, cellular-targeted therapeutic interventions potential treating Overall, we emphasize critical role health managing COVID highlight need early intervention prevent long-term dysfunction.

Язык: Английский

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Molecular Mimicry and HLA Polymorphisms May Drive Autoimmunity in Recipients of the BNT-162b2 mRNA Vaccine: A Computational Analysis

Microorganisms, Год журнала: 2023, Номер 11(7), С. 1686 - 1686

Опубликована: Июнь 28, 2023

After the start of worldwide COVID-19 vaccination campaign, there were increased reports autoimmune diseases occurring de novo after vaccination. This in silico analysis aimed to investigate presence protein epitopes encoded by BNT-162b2 mRNA vaccine, one most widely administered vaccines, which could induce autoimmunity predisposed individuals.The FASTA sequence vaccine served as key input Immune Epitope Database and Analysis Resource. Linear peptides with 90% BLAST homology selected, T-cell, B-cell, MHC-ligand assays without MHC restriction searched analyzed. HLA disease associations screened on HLA-SPREAD platform selecting only positive markers.By 7 May 2023, a total 5693 corresponding 21 viral but also human proteins found. The latter included CHL1, ENTPD1, MEAF6, SLC35G2, ZFHX2. Importantly, some autoepitopes may be presented alleles positively associated various immunological diseases.The product contains immunogenic that trigger phenomena individuals through molecular mimicry mechanism. Genotyping for help identify at risk. However, further wet-lab studies are needed confirm this hypothesis.

Язык: Английский

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