Interaction of SARS-CoV-2 with host cells and antibodies: experiment and simulation

Chemical Society Reviews, Journal Year: 2023, Volume and Issue: 52(18), P. 6497 - 6553

Published: Jan. 1, 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of devastating global COVID-19 pandemic announced by WHO in March 2020.

Language: Английский

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Is neuropilin-1 the neuroimmune initiator of multi-system hyperinflammation in COVID-19?

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 167, P. 115558 - 115558

Published: Sept. 23, 2023

A major immunopathological feature of Coronavirus disease-2019 (COVID-19) is excessive inflammation in the form "cytokine storm". The storm characterized by injurious levels cytokines which a complicated network damaging different organs, including lungs and brain. main starter network" hyperactivation COVID-19 has not been discovered yet. Neuropilins (NRPs) are transmembrane proteins that act as neuronal guidance angiogenesis modulators. crucial function NRPs forming nervous vascular systems well-studied. NRP1 NRP2 two identified homologs NRP. shown viral entry pathway for SARS-CoV2, facilitates neuroinvasion virus within central or peripheral systems. These molecules directly interact with various COVID-19-related molecules, such specific regions spike protein (major immune element SARS-CoV2), endothelial growth factor (VEGF) receptors, VEGFR1/2, ANGPTL4 (regulator vessel permeability integrity). mainly play role hyperinflammatory injury CNS lungs, also liver, kidney, pancreas, heart patients. New findings have suggested good candidates pharmacotherapy COVID-19. However, therapeutic targeting still preclinical phase. This review presents implications multi-organ inflammation-induced SARS-CoV2 provides insights NRP1-targeting treatments

Language: Английский

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Single-virus tracking reveals variant SARS-CoV-2 spike proteins induce ACE2-independent membrane interactions

Science Advances, Journal Year: 2022, Volume and Issue: 8(49)

Published: Dec. 9, 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became a global health crisis after its emergence in 2019. Replication of the virus is initiated by binding viral spike (S) protein to human angiotensin-converting enzyme (ACE2) on target cell surface. Mutations acquired SARS-CoV-2 S variants likely influence virus-target interaction. Here, using single-virus tracking capture these initial steps, we observe how viruses carrying variant interact with cells. Specificity for ACE2 occurs reference sequence or D614G mutation. Analysis Alpha, Beta, and Delta proteins revealed progressive altered interaction reduced dependence ACE2. Notably, affinity was independent These enhanced interactions may account increased transmissibility variants. Knowledge mutations essential vaccine development against emerging SARS-CoV-2.

Language: Английский

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The role of DNA methylation in personalized medicine for immune-related diseases

Pharmacology & Therapeutics, Journal Year: 2023, Volume and Issue: 250, P. 108508 - 108508

Published: Aug. 9, 2023

Language: Английский

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An Overview of SARS-CoV-2 Potential Targets, Inhibitors, and Computational Insights to Enrich the Promising Treatment Strategies

Current Microbiology, Journal Year: 2024, Volume and Issue: 81(7)

Published: May 11, 2024

Language: Английский

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Revealing the Hidden Impacts: Insights into Biological Aging and Long-Term Effects in Pauci- and Asymptomatic COVID-19 Healthcare Workers

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(15), P. 8056 - 8056

Published: July 24, 2024

This study explores the role of inflammation and oxidative stress, hallmarks COVID-19, in accelerating cellular biological aging. We investigated early molecular markers—DNA methylation age (DNAmAge) telomere length (TL)—in blood leukocytes, nasal cells (NCs), induced sputum (IS) one year post-infection pauci- asymptomatic healthcare workers (HCWs) infected during first pandemic wave (February–May 2020), compared to COPD patients, model for “aged lung”. Data from questionnaires, Work Ability Index (WAI), analyses, autonomic cardiac balance assessments, heart rate variability (HRV), pulmonary function tests were collected. Elevated leukocyte DNAmAge significantly correlated with advancing age, male sex, daytime work, an aged phenotype characterized by chronic diseases, elevated LDL glycemia levels, medications affecting HRV, declines lung function, WAI, lymphocyte count, hemoglobin HRV (p < 0.05). Increasing job positions involving intensive patient contact, higher counts collectively contributed shortened TL Notably, HCWs exhibited accelerated aging IS both leukocytes ≤ 0.05) NCs 0.001) biologically older than patients These findings suggest need monitor COVID-19 survivors, who represent majority general population.

Language: Английский

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Valproic acid use is associated with diminished risk of contracting COVID-19, and diminished disease severity: Epidemiologic and in vitro analysis reveal mechanistic insights

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(8), P. e0307154 - e0307154

Published: Aug. 2, 2024

The SARS-CoV-2 pandemic has caused unprecedented worldwide infections from persistent mutant variants with various degrees of infectivity and virulence. elusiveness a highly penetrant, vaccination strategy suggests that the complete eradication is unlikely. Even advent new antiviral agents, disease burden continues to exceed current preventative therapeutic strategies. Greater interest been placed towards development affordable,broadly effective therapeutics. Here, we report small branched-chain fatty acid Valproic (VPA), approved for maintenance seizure bipolar disorder, novel anti- coronavirus activity can be augmented addition long-chain, polyunsaturated omega-3 acid, Docosahexaenoic (DHA). An EMR-based epidemiological study patients tested COVID-19 demonstrated correlation exists between reduced infection rate in treated withVPA up 25%, as well decreased risk emergency room visits, hospitalization, ICU admission,and use mechanical ventilation. In vitro studies have VPA modifies gene expression MRC5 cells. Interestingly, correlates inhibition several SARS-CoV2 interacting genes greater alpha-coronavirus HCoV-229E (a “common cold” virus) SARS-CoV2. VPA-DHA combination activates pre-existing intracellular mechanisms normally repressed by coronaviruses. Gene profiles demonstrate subtle differences overall VPA-treated VPA-DHA-treated an intensely different response marked induction multiple inflammatory genes. Changes took at least 24 hours manifest most likely why prior drug screens failed identify any despite silico predictions. This demonstrates interaction HDAC potent activation cellular responses. A foundation now low-cost, when supplemented DHA.

Language: Английский

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HDAC1-3 inhibition increases SARS-CoV-2 replication and productive infection in lung mesothelial and epithelial cells

Frontiers in Cellular and Infection Microbiology, Journal Year: 2023, Volume and Issue: 13

Published: Dec. 13, 2023

Background Despite the significant progress achieved in understanding pathology and clinical management of SARS-CoV-2 infection, still pathogenic issues need to be clarified. Treatment with modulators epigenetic targets, i.e., epidrugs, is a current therapeutic option several cancers could represent an approach therapy viral diseases. Results Aim this study was analysis role histone deacetylase (HDAC) inhibition modulation infection mesothelial cells (MCs). MeT5A cells, pleura MC line, were pre-treated different specific class I IIb HDAC inhibitors. Unexpectedly, treatment HDAC1-3 inhibitors significantly increased ACE2/TMPRSS2 expression, suggesting favoring infection. We focused our on most potent inducer among analysed, MS-275, inhibitor. expression validated by Western Blot (WB) immunofluorescence. The involvement receptor induction confirmed HDAC1/HDAC2 silencing. In accordance data, MS-275 replication virus propagation Vero E6 cells. Notably, able increase production, although lesser extent, also lung adenocarcinoma cell line Calu-3 Mechanistically, H3 H4 acetylation at promoters, increasing their transcription. Conclusion This highlights previously unrecognized effect entry, productive correlating ACE2 TMPRSS2. These while adding basic insight into COVID-19 pathogenesis, warn for use patients.

Language: Английский

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Exposure to valproic acid is associated with less pulmonary infiltrates and improvements in diverse clinical outcomes and laboratory parameters in patients hospitalized with COVID-19

PLoS ONE, Journal Year: 2022, Volume and Issue: 17(1), P. e0262777 - e0262777

Published: Jan. 27, 2022

Valproic acid (VPA) has shown beneficial effects in vitro against SARS-CoV-2 infection, but no study analyzed its efficacy the clinical setting.This multicenter, retrospective included 165 adult patients receiving VPA at time of admission to hospital, and 330 controls matched for sex, age date admission. A number clinical, outcome laboratory parameters were recorded evaluate differences between two groups. Four major endpoints considered: development lung infiltrates, in-hospital respiratory worsening, ICU admissions death.VPA-treated had higher lymphocyte (P<0.0001) monocyte (P = 0.0002) counts, lower levels diverse inflammatory parameters, including a composite biochemical severity score 0.016). shorter duration symptoms (P<0.0001), more commonly asymptomatic 0.016), developed less infiltrates (65.8%/88.2%, P<0.0001), worsening (20.6%/30.6%, P 0.019) (6.1%/13.0%, 0.018). There was difference survival (84.8%/88.8%, 0.2), although death related non-COVID-19 causes group (36.0%/10.8%, 0.017). The cumulative hazard developing adverse than 0.001), not (0.6). Multivariate analysis revealed that treatment independently protective first three 0.0002, 0.03, 0.025, respectively), 0.2).VPA-treated seem develop serious COVID-19 control patients, according markers.

Language: Английский

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C3aR in astrocytes mediates post-thoracotomy pain by inducing A1 astrocytes in male rats

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2023, Volume and Issue: 1869(5), P. 166672 - 166672

Published: March 5, 2023

Language: Английский

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