Mechanisms of action of fluvoxamine for COVID-19: a historical review

Molecular Psychiatry, Journal Year: 2022, Volume and Issue: 27(4), P. 1898 - 1907

Published: Jan. 7, 2022

Language: Английский

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Integrated multi-omics analyses identify anti-viral host factors and pathways controlling SARS-CoV-2 infection

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 2, 2024

Host anti-viral factors are essential for controlling SARS-CoV-2 infection but remain largely unknown due to the biases of previous large-scale studies toward pro-viral host factors. To fill in this knowledge gap, we perform a genome-wide CRISPR dropout screen and integrate analyses multi-omics data screen, association studies, single-cell RNA-Seq, host-virus proteins or protein/RNA interactome. This study uncovers many that currently underappreciated, including components V-ATPases, ESCRT, N-glycosylation pathways modulate viral entry and/or replication. The cohesin complex is also identified as an pathway, suggesting important role three-dimensional chromatin organization mediating host-viral interaction. Furthermore, discover another regulator KLF5, transcriptional factor involved sphingolipid metabolism, which up-regulated, harbors genetic variations linked COVID-19 patients with severe symptoms. Anti-viral effects three candidates (DAZAP2/VTA1/KLF5) confirmed individually. Molecular characterization DAZAP2/VTA1/KLF5-knockout cells highlights involvement genes related coagulation system determining severity COVID-19. Together, our results provide further resources understanding network during may help develop new countermeasure strategies.

Language: Английский

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Severity of COVID-19 Patients Predicted by Serum Sphingolipids Signature

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(19), P. 10198 - 10198

Published: Sept. 22, 2021

The reason behind the high inter-individual variability in response to SARS-CoV-2 infection and patient’s outcome is poorly understood. present study targets sphingolipid profile of twenty-four healthy controls fifty-nine COVID-19 patients with different disease severity. Sera were analyzed by untargeted targeted mass spectrometry ELISA. Results indicated a progressive increase dihydrosphingosine, dihydroceramides, ceramides, sphingosine, decrease sphingosine-1-phosphate. These changes are associated serine palmitoyltransferase long chain base subunit 1 (SPTLC1) relation Severe showed sphingomyelins level acid sphingomyelinase (aSMase) that influences monosialodihexosyl ganglioside (GM3) C16:0 levels. Critical characterized levels dihydrosphingosine dihydroceramide but not glycosphingolipids. In severe critical patients, unbalanced lipid metabolism induces raft remodeling, leads cell apoptosis immunoescape, suggesting active participation viral infection. Furthermore, results glycosphingolipid metabolic rewiring promoted aSMase GM3 age-dependent also characteristic influencing prognosis increasing load. AUCs calculated from ROC curves ceramides C16:0, C18:0, C24:1, sphingosine SPTLC1 as putative biomarkers evolution.

Language: Английский

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Simvastatin Downregulates the SARS-CoV-2-Induced Inflammatory Response and Impairs Viral Infection Through Disruption of Lipid Rafts

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Feb. 18, 2022

Coronavirus disease 2019 (COVID-19) is currently a worldwide emergency caused by Severe Acute Respiratory Syndrome 2 (SARS-CoV-2). In observational clinical studies, statins have been identified as beneficial to hospitalized patients with COVID-19. However, experimental evidence of underlying protection against SARS-CoV-2 remains elusive. Here we reported for the first-time protective effects simvastatin treatment both in vitro and vivo . We found that significantly reduced viral replication lung damage , delaying SARS-CoV-2-associated physiopathology mortality K18-hACE2-transgenic mice model. Moreover, also downregulated inflammation triggered infection pulmonary tissue human neutrophils, peripheral blood monocytes, epithelial Calu-3 cells showing its potential modulate inflammatory response at site systemically. Additionally, observed affected course through displacing ACE2 on cell membrane lipid rafts. conclusion, our results show exhibits early inhibiting virus entry cytokine production, mechanisms least part dependent rafts disruption.

Language: Английский

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Lipid Raft Integrity and Cellular Cholesterol Homeostasis Are Critical for SARS-CoV-2 Entry into Cells

Nutrients, Journal Year: 2022, Volume and Issue: 14(16), P. 3417 - 3417

Published: Aug. 19, 2022

Lipid rafts in cell plasma membranes play a critical role the life cycle of many viruses. However, involvement membrane cholesterol-rich lipid entry severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into target cells is not well known. In this study, we investigated whether presence microdomains required for SARS-CoV-2 host cells. Our results show that depletion cholesterol by methyl-beta-cyclodextrin (MβCD) treatment impaired expression surface receptor angiotensin-converting enzyme (ACE2), resulting significant increase The effects exerted MβCD could be substantially reversed exogenous replenishment. contrast, disturbance intracellular homeostasis statins or siRNA knockdown key genes involved biosynthesis and transport pathways reduced study also reveals SREBP2-mediated process These suggest cholesterol-enriched cellular are essential Pharmacological manipulation might provide new therapeutic strategies to alleviate

Language: Английский

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Sphingolipid-Induced Bone Regulation and Its Emerging Role in Dysfunction Due to Disease and Infection

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(5), P. 3024 - 3024

Published: March 5, 2024

The human skeleton is a metabolically active system that constantly regenerating via the tightly regulated and highly coordinated processes of bone resorption formation. Emerging evidence reveals fascinating new insights into role sphingolipids, including sphingomyelin, sphingosine, ceramide, sphingosine-1-phosphate, in homeostasis. Sphingolipids are major class bioactive lipids able to activate distinct protein targets including, lipases, phosphatases, kinases, thereby conferring cellular functions beyond energy metabolism. Lipids known contribute progression chronic inflammation, notably, an increase marrow adiposity parallel elevated loss observed most pathological conditions, aging, rheumatoid arthritis, osteoarthritis, osteomyelitis. Of numerous classes form, sphingolipids considered among deleterious. This review highlights important primary homeostasis how dysregulation these metabolites appears central many bone-related diseases. Further, their contribution invasion, virulence, colonization both viral bacterial host cell infections also discussed. Many unmet clinical needs remain, data date suggest future use sphingolipid-targeted therapy regulate dysfunction due variety diseases or infection promising. However, deciphering biochemical molecular mechanisms this diverse extremely complex sphingolipidome, terms health disease, next frontier field.

Language: Английский

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Precision nutrition to reset virus-induced human metabolic reprogramming and dysregulation (HMRD) in long-COVID

npj Science of Food, Journal Year: 2024, Volume and Issue: 8(1)

Published: March 30, 2024

Language: Английский

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Analysis of the impact of antidepressants and other medications on COVID-19 infection risk in a chronic psychiatric in-patient cohort

BJPsych Open, Journal Year: 2021, Volume and Issue: 8(1)

Published: Dec. 3, 2021

During the first wave of coronavirus disease 2019 (COVID-19) pandemic, patients with confirmed cases in New York State accounted for roughly 25% total US cases, psychiatric hospital in-patients at particularly high risk COVID-19 infection.The beneficial effects mental health medications, such as selective serotonin reuptake inhibitors (SSRIs), on severity outcomes have been documented. Protective against infection also suggested these medications. We therefore tested hypothesis that medication use modifies a long-stay, chronic in-patient psychiatry setting, where potential exposure was likely uniform across facility, and medications were routinely prescribed.This retrospective cohort study an adult facility operated by Office Mental Health. Current information status collected from electronic medical records 165 people who during period January to July 2020, logistic regression employed model main infection.A significant protective association observed between antidepressant (odds ratio (OR) = 0.33, 95% CI 0.15-0.70, adjusted P < 0.05). Analysis individual classes showed SSRI, serotonin-norepinephrine inhibitor serotonin-2 antagonist antidepressants, drove this effect. Exploratory analyses antidepressants demonstrated lower fluoxetine (P 0.023), well trazodone 0.001).The novel finding reduced taking suggests may be important weapon continued fight disease. This become salient settings if vaccine-resistant strains virus appear.

Language: Английский

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Characterization of oral and gut microbiome and plasma metabolomics in COVID-19 patients after 1-year follow-up

Military Medical Research, Journal Year: 2022, Volume and Issue: 9(1)

Published: June 17, 2022

Abstract Background Due to the outbreak and rapid spread of coronavirus disease 2019 (COVID-19), more than 160 million patients have become convalescents worldwide date. Significant alterations occurred in gut oral microbiome metabonomics with COVID-19. However, it is unknown whether their characteristics return normal after 1-year recovery. Methods We recruited 35 confirmed provide specimens at discharge one year later, as well healthy controls. A total 497 samples were prospectively collected, including 219 tongue-coating, 129 stool 149 plasma samples. Tongue-coating subjected 16S rRNA sequencing, untargeted metabolomics testing. Results The restored a large extent but did not completely normal. In recovery process, microbial diversity gradually increased. Butyric acid-producing microbes Bifidobacterium increased, whereas lipopolysaccharide-producing decreased. addition, sphingosine-1-phosphate, which closely related inflammatory factor storm COVID-19, increased significantly during process. Moreover, predictive models established based on metabolites time reached high efficacy predicting neutralizing antibody levels later. Conclusions This study first characterize key process identified, provided new treatment ideas for accelerating And afford insights situation benefited affected individuals healthcare.

Language: Английский

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Overview of the potential use of fluvoxamine for COVID-19 and long COVID

Discover Mental Health, Journal Year: 2023, Volume and Issue: 3(1)

Published: March 21, 2023

Abstract Coronavirus disease 2019 (COVID-19) has presented a serious worldwide threat to public health since its emergence in late 2019. From safety point of view, drug repurposing received particular attention. Several clinical studies have demonstrated that the use fluvoxamine, selective serotonin reuptake inhibitor with potent sigma-1 receptor agonism, early-stage infection might be associated prevention deterioration individuals SARS-CoV-2 infection, although several reports shown low dose fluvoxamine may ineffective. There is increasing evidence can cross blood–brain barrier, resulting number psychiatric and neurologic symptoms COVID-19 survivors. Importantly, about half survivors experience variety long-term sequelae, including symptoms, known as long COVID. In this priority review, author presents an overview potential treatment

Language: Английский

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