Circulating microRNA signatures associated with disease severity and outcome in COVID-19 patients

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

Published: Aug. 11, 2022

SARS-CoV-2 induces a spectrum of clinical conditions ranging from asymptomatic infection to life threatening severe disease. Host microRNAs have been involved in the cytokine storm driven by and proposed as candidate biomarkers for COVID-19.

Language: Английский

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SARS-CoV-2 Nsp14 mediates the effects of viral infection on the host cell transcriptome

eLife, Journal Year: 2022, Volume and Issue: 11

Published: March 16, 2022

Viral infection involves complex set of events orchestrated by multiple viral proteins. To identify functions SARS-CoV-2 proteins, we performed transcriptomic analyses cells expressing individual Expression Nsp14, a protein involved in RNA replication, provoked dramatic remodeling the transcriptome that strongly resembled observed following infection. Moreover, Nsp14 expression altered splicing more than 1000 genes and resulted increase number circRNAs, which are linked to innate immunity. These effects were independent exonuclease activity required N7-guanine-methyltransferase domain protein. Activation NFkB pathway increased CXCL8 occurred early upon expression. We identified IMPDH2, catalyzes rate-limiting step guanine nucleotides biosynthesis, as key mediator these effects. caused an GTP cellular levels, effect was decreased presence IMPDH2 inhibitors. Together, our data demonstrate unknown role for with implications therapy.Viruses parasites, relying on they infect make themselves. In doing so change how infected cell turns its off, forcing it build new virus particles turning off immune surveillance would allow body intervene. This is SARS-CoV-2, causes COVID, survives genome carries instructions just 29 One known both reproduction escape. Previous work has shown interacts enzyme controls production building blocks genetic code. The impact this interaction not clear. find out more, Zaffagni et al. introduced 26 proteins into human one at time. had most effect, dialing around 4,000 up or down changing interprets over 1,000 genes. Despite being protein, mimicked changes seen during real Blocking partially reversed effects, suggests might be responsible cell. Understanding affect can explain what happens could lead discovery treatments designed counteract virus. Further investigate whether interfering helps overcome

Language: Английский

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Generation and Functional Analysis of Defective Viral Genomes during SARS-CoV-2 Infection

mBio, Journal Year: 2023, Volume and Issue: 14(3)

Published: April 19, 2023

Defective viral genomes (DVGs) are generated ubiquitously in many RNA viruses, including SARS-CoV-2. Their interference activity to full-length viruses and IFN stimulation provide the potential for them be used novel antiviral therapies vaccine development.

Language: Английский

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Following the design path of isoform-selective Hsp90 inhibitors: Small differences, great opportunities

Pharmacology & Therapeutics, Journal Year: 2023, Volume and Issue: 245, P. 108396 - 108396

Published: March 29, 2023

The heat shock protein 90 (Hsp90) family consists of four highly conserved isoforms: the mitochondrial TRAP-1, endoplasmic reticulum-localised Grp94, and cytoplasmic Hsp90α Hsp90β. Since late 1990s, this has been extensively studied as a potential target for treatment cancer, neurological disorders, infectious diseases. initial approach was to develop non-selective, so-called pan-Hsp90 ATP-competitive inhibitors N-terminal domain. Many these agents were tested in clinical trials, mainly but none them succeeded clinic. This due lack efficacy various toxicities associated with induction response (HSR). success prompted turn new approaches Hsp90 inhibition. Thus, selective particular isoform have developed. These isoform-selective do not induce HSR more targeted effect because all client proteins are equally dependent on paralogues Hsp90. However, it is extremely difficult such compounds conserved. Hsp90β an amazing 95% identity ATP binding site, differing only two amino acid residues. Therefore, focus review fully elucidate key structural features inhibitor classes terms site dissimilarities. In addition methodological characterisation structure-activity relationships, main advantages inhibition isoforms discussed.

Language: Английский

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SARS-CoV-2 Spike Protein Accumulation in the Skull-Meninges-Brain Axis: Potential Implications for Long-Term Neurological Complications in post-COVID-19

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: April 5, 2023

ABSTRACT Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), has been associated mainly with a range of neurological symptoms, including brain fog and tissue loss, raising concerns about virus’s potential chronic impact on central nervous system. In this study, we utilized mouse models human post-mortem tissues to investigate presence distribution SARS-CoV-2 spike protein in skull-meninges-brain axis. Our results revealed accumulation skull marrow, meninges, parenchyma. The injection alone cell death brain, highlighting direct effect tissue. Furthermore, observed deceased long after their COVID-19 infection, suggesting that spike’s persistence may contribute long-term symptoms. was neutrophil-related pathways dysregulation proteins involved PI3K-AKT as well complement coagulation pathway. Overall, our findings suggest trafficking from CNS borders into parenchyma identified differentially regulated present insights mechanisms underlying immediate consequences diagnostic therapeutic opportunities. Graphical Summary Short axis presents molecular targets for complications long-COVID-19 patients .

Language: Английский

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