Convergent Evolution Dynamics of SARS-CoV-2 and HIV Surface Envelope Glycoproteins Driven by Host Cell Surface Receptors and Lipid Rafts: Lessons for the Future

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(3), С. 1923 - 1923

Опубликована: Янв. 18, 2023

Although very different, in terms of their genomic organization, enzymatic proteins, and structural HIV SARS-CoV-2 have an extraordinary evolutionary potential common. Faced with various selection pressures that may be generated by treatments or immune responses, these RNA viruses demonstrate high adaptive capacities, which result the continuous emergence variants quasi-species. In this retrospective analysis viral ensuring adhesion to plasma membrane host cells, we highlight many common points suggest convergent mechanisms evolution. first recognize a lipid raft microdomain acts as landing strip for particles on cell surface. case mucosal are primary targets both viruses, microdomains enriched anionic glycolipids (gangliosides) forming global electronegative field. Both use rafts surf surface search protein receptor able trigger fusion process. This implies envelope proteins geometrically electrically compatible biomolecules they select invade cells. present study, identify electrostatic critical parameter controlling evolution dynamics HIV-1 discuss impact phenotypic properties viruses. The virological data accumulated since early 1980s should help us face future virus pandemics.

Язык: Английский

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Association between lipid profile and clinical outcomes in COVID-19 patients

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Май 27, 2024

Abstract High-density lipoprotein cholesterol (HDL-c) removes cholesterol, an essential component in lipid rafts, and this removal can regulate protein attachment to modulating their functionality the immune cell response. Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection alter profile, there is little information on role of HDL-c other lipids prognostic disease 2019 (COVID-19) Mexican population. This study aims evaluate predictive value profile severity survival 102 patients infected with SARS-CoV-2 during COVID-19 first wave. Our findings, derived from univariate multivariate Cox proportional hazards regression models, highlighted age hypertension as significant predictors (HR = 1.04, p 0.012; HR 2.78, 0.027), while gender, diabetes, obesity showed no impact. Triglycerides levels notably influenced mortality, elevated triglycerides lower associated higher mortality risk (p 0.032). underscores importance profiles alongside traditional factors assessing outcomes. It contributes understanding patient management emphasizes need for further investigation into dyslipidemia influencing prognosis, potentially aiding refined stratification therapeutic strategies.

Язык: Английский

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SARS-CoV-2-associated lymphopenia: possible mechanisms and the role of CD147

Cell Communication and Signaling, Год журнала: 2024, Номер 22(1)

Опубликована: Июль 4, 2024

T lymphocytes play a primary role in the adaptive antiviral immunity. Both lymphocytosis and lymphopenia were found to be associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While indicates an active anti-viral response, is sign of poor prognosis. T-cells, essence, rarely express ACE2 receptors, making cause cell depletion enigmatic. Moreover, emerging strains posed immunological challenge, potentially alarming for next pandemic. Herein, we review how possible indirect direct key mechanisms could contribute SARS-CoV-2-associated-lymphopenia. The fundamental mechanism inflammatory cytokine storm elicited by viral infection, which alters host metabolism into more acidic state. This "hyperlactic acidemia" together suppresses T-cell proliferation triggers intrinsic/extrinsic apoptosis. SARS-CoV-2 infection also results shift from steady-state hematopoiesis stress hematopoiesis. Even low expression, presence cholesterol-rich lipid rafts on activated T-cells may enhance entry syncytia formation. Finally, indicate participation other receptors or auxiliary proteins that can work alone concert mechanisms. Therefore, address CD147-a novel route-for its new variants. CD147 not only expressed but it interacts co-partners orchestrate various biological processes. Given these features, appealing candidate pathogenicity. Understanding molecular cellular behind SARS-CoV-2-associated-lymphopenia will aid discovery potential therapeutic targets improve resilience our immune system against this rapidly evolving virus.

Язык: Английский

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The Association Between the Gut Microbiome and COVID-19 Severity: The Potential Role of TMAO Produced by the Gut Microbiome

Archives of Clinical Infectious Diseases, Год журнала: 2024, Номер 18(6)

Опубликована: Янв. 1, 2024

Context: The COVID-19 pandemic has had profound impacts on public health, resulting in nearly 1 million deaths. Emerging evidence suggests an association between certain metabolites produced by gut microbiota and potential alterations the severity of infection. Trimethylamine N-oxide (TMAO) is a waste metabolite generated microbes from dietary choline betaine. Evidence Acquisition: Several investigations have indicated serum TMAO concentrations development inflammation thrombosis. N-oxide, microbiome state dysbiosis, upregulates various molecular mechanisms, such as nuclear factor kappa (NF-kB) pathway, promotes expression scavenger receptors (SRs) surfaces macrophages, leading to foam cell formation inflammation. High levels been shown induce pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF-α) interleukin 1β (IL-1β) while reducing anti-inflammatory interleukin-10 (IL-10). Additionally, gut-derived enhances platelet aggregation adhesion collagen, increasing risk Conclusions: Understanding compositions their effects SARS-CoV-19 infection progression helps control disease severity. In this review, we presented hypothesis that increase

Язык: Английский

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HDL-based therapeutics: A promising frontier in combating viral and bacterial infections

Pharmacology & Therapeutics, Год журнала: 2024, Номер 260, С. 108684 - 108684

Опубликована: Июль 2, 2024

Язык: Английский

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Veklury® (remdesivir) formulations inhibit initial membrane‐coupled events of SARS‐CoV‐2 infection due to their sulfobutylether‐β‐cyclodextrin content

British Journal of Pharmacology, Год журнала: 2023, Номер 180(16), С. 2064 - 2084

Опубликована: Фев. 27, 2023

Despite its contradictory clinical performance, remdesivir (Veklury®) has a pivotal role in COVID-19 therapy. Possible contributions of the vehicle, sulfobutylether-β-cyclodextrin (SBECD) to Veklury® effects have been overlooked. The powder and solution formulations are treated equivalently despite their different vehicle content. Our objective was study on initial membrane-coupled events SARS-CoV-2 infection focusing cholesterol depletion-mediated SBECD.Using time-correlated flow cytometry quantitative three-dimensional confocal microscopy, we studied early molecular SARS-CoV-2-host cell membrane interactions.Veklury® cholesterol-depleting cyclodextrins (CDs) reduced binding spike receptor-binding domain (RBD) ACE2 trimer internalization for Wuhan-Hu-1, Delta Omicron variants. Correlations these with cholesterol-dependent changes structure decreased lipid raft-dependent ACE2-TMPRSS2 interaction establish that SBECD is not simply but also an effector along due potential. inhibited RBD more efficiently twice higher CD-induced inhibitory were prominent at lower concentrations cells endogenous expression, indicating supportive CD actions can be even pronounced during vivo when viral load ACE expression typically low.Our findings call differentiation meta-analyses trials, potentially revealing neglected benefits formulation, raise possibility adjuvant cyclodextrin (CD) therapy, doses, COVID-19.

Язык: Английский

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Host Membranes as Drivers of Virus Evolution

Viruses, Год журнала: 2023, Номер 15(9), С. 1854 - 1854

Опубликована: Авг. 31, 2023

The molecular mechanisms controlling the adaptation of viruses to host cells are generally poorly documented. An essential issue resolve is whether membranes, and especially lipid rafts, which usually considered passive gateways for many enveloped viruses, also encode informational guidelines that could determine virus evolution. Due their enrichment in gangliosides confer an electronegative surface potential, rafts impose a first control level favoring selection with enhanced cationic areas, as illustrated by SARS-CoV-2 variants. Ganglioside clusters attract viral particles dynamic electrostatic funnel, more population winning race. However, forces account only small part energy raft-virus interaction, depends mainly on ability form network hydrogen bonds raft gangliosides. This fine tuning virus-ganglioside interactions, stabilize membrane, generates second pressure driven typical induced-fit mechanism. Gangliosides play active role this process, wrapping around spikes through quicksand-like Viruses thus endless race access they bound evolve perpetually, combining speed (electrostatic potential) precision (fine amino acids) under selective immune system. Deciphering membrane evolution may open new avenues design innovative antivirals.

Язык: Английский

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Smoking and vaping alter genes related to mechanisms of SARS-CoV-2 susceptibility and severity

European Respiratory Journal, Год журнала: 2024, Номер 64(1), С. 2400133 - 2400133

Опубликована: Июль 1, 2024

Background Evidence for the impact of smoking on coronavirus disease 2019 (COVID-19) is contradictory, and there little research vaping. Here we provide greater clarity mechanisms perturbed by tobacco cigarette, electronic cigarette nicotine exposures that may risks infection and/or severity. Methods Following Preferred Reporting Items Systematic Reviews Meta-Analyses (PRISMA) guidelines, Ovid Web Science databases were searched. Study design exposure-induced gene expression changes extracted. Each study was quality assessed higher confidence scores assigned to genes consistently changed across multiple studies following same exposure. These used explore pathways significantly altered Results 125 provided data 480 exposure cigarettes, e-cigarettes, or severe acute respiratory syndrome 2 (SARS-CoV-2). Genes involved in both SARS-CoV-2 viral-entry inflammation Pathway analysis revealed many those with high are common cellular processes relating hyperinflammatory immune responses. Conclusion Exposure e-cigarettes therefore initial host–pathogen interactions Smokers vapers could potentially be at increased risk infection, associated cytokine storm, distress syndrome. However, further required, particularly determine biological perturbation subsequent responses within tract. This will improve our physiological understanding vaping COVID-19, informing public health advice providing improved guidance management other viruses.

Язык: Английский

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Cholesterol-rich lysosomes induced by respiratory syncytial virus promote viral replication by blocking autophagy flux

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Июль 26, 2024

Abstract Respiratory syncytial virus (RSV) hijacks cholesterol or autophagy pathways to facilitate optimal replication. However, our understanding of the associated molecular mechanisms remains limited. Here, we show that RSV infection blocks transport from lysosomes endoplasmic reticulum by downregulating activity lysosomal acid lipase, activates SREBP2–LDLR axis, and promotes uptake accumulation exogenous in lysosomes. High levels impair VAP-A-binding ORP1L promote recruitment dynein–dynactin, PLEKHM1, HOPS VPS39 Rab7–RILP, thereby facilitating minus-end autophagosomes autolysosome formation. Acidification inhibition dysfunction cholesterol-rich flux inhibiting degradation, which fusion protein. RSV-F storage is nearly abolished after depletion knockdown LDLR. Most importantly, knockout LDLR effectively inhibits vivo. These findings elucidate mechanism how co-regulates reprogramming reveal as a novel target for anti-RSV drug development.

Язык: Английский

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Treatment of COVID‐19‐Associated Ageusia and Xerostomia

Oral Diseases, Год журнала: 2025, Номер unknown

Опубликована: Фев. 10, 2025

Язык: Английский

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