Predicting host-based, synthetic lethal antiviral targets from omics data DOI Creative Commons
Jeannette P. Staheli, M J Neal, Arti T. Navare

et al.

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

Published: Aug. 16, 2023

Traditional antiviral therapies often have limited effectiveness due to toxicity and development of drug resistance. Host-based antivirals, while an alternative, may lead non-specific effects. Recent evidence shows that virus-infected cells can be selectively eliminated by targeting synthetic lethal (SL) partners proteins disrupted viral infection. Thus, we hypothesized genes depleted in CRISPR KO screens enriched SL altered To investigate this, established a computational pipeline predicting targets infections. First, identified SARS-CoV-2-induced changes gene products via large compendium omics data. Second, for each product. Last, screened data required cell viability infected cells. Despite differences virus-induced alterations detected various data, they share many predicted targets, with significant enrichment KO-depleted datasets. Comparing from SARS-CoV-2 influenza infections, found possible broad-spectrum, host-based targets. This suggests are replete common their relationship virus-altered states such revealed analysis datasets predictions.

Language: Английский

Integrated multi-omics analysis reveals liver metabolic reprogramming by fish iridovirus and antiviral function of alpha-linolenic acid DOI Open Access
Lin Liu, Ya Zhang,

Meng-Di Yuan

et al.

动物学研究, Journal Year: 2024, Volume and Issue: 45(3), P. 520 - 534

Published: Jan. 1, 2024

Iridovirus has become a great threat to global aquaculture due its high mortality, while the molecular events in virus pathogenesis are not well elucidated. Here, multi-omics approach was performed with Singapore grouper iridovirus (SGIV)-infected groupers, and roles of key metabolites were investigated. SGIV induced obvious histopathological damage changes metabolic enzymes liver. Besides, significantly decreased contents lipid droplets, triglycerides, cholesterol, lipoprotein. Metabolome analysis showed that differentially enriched 19 pathways, metabolites, including glycerophosphates alpha-linolenic acid (ALA) down-regulated, which is consistent disturbed homeostasis Combining transcriptomic metabolomic data, top pathways related cell growth death, nucleotide, carbohydrate, amino acid, metabolisms, supporting conclusion infection liver reprogramming. Integrative proteomic indicated activated crucial phagosome-immune depression-metabolism dysregulation-necrosis signaling cascade. Of note, integrative demonstrated ALA linoleic (LA) consumed, L-glutamic (GA) accumulated, accompanied by alteration immune, inflammation, death genes. Further experimental data ALA, but GA suppressed replication activating host antioxidant anti-inflammatory effects. Together, our findings for first time provide comprehensive resource understand landscape response dynamics during fish infection, highlight antiviral prevention treatment diseases.

Language: Английский

Citations

13
Membrane remodeling and trafficking piloted by SARS-CoV-2 DOI Creative Commons

Maria Concetta Sergio,

Simona Ricciardi, Andrea Maria Guarino

et al.

Trends in Cell Biology, Journal Year: 2024, Volume and Issue: 34(9), P. 785 - 800

Published: Jan. 22, 2024

The molecular mechanisms underlying SARS-CoV-2 host cell invasion and life cycle have been studied extensively in recent years, with a primary focus on viral entry internalization the aim of identifying antiviral therapies. By contrast, our understanding involved later steps coronavirus is relatively limited. In this review, we describe what known about factors proteins replication, assembly, egress phases SARS-CoV-2, which induce significant membrane rearrangements. We also discuss limits current approaches knowledge gaps still to be addressed.

Language: Английский

Citations

12
The cGAS-STING pathway in viral infections: a promising link between inflammation, oxidative stress and autophagy DOI Creative Commons
Kunli Zhang,

Qiuyan Huang,

Xinming Li

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 15, 2024

The host defence responses play vital roles in viral infection and are regulated by complex interactive networks. immune system recognizes pathogens through the interaction of pattern-recognition receptors (PRRs) with pathogen-associated molecular patterns (PAMPs). As a PRR mainly cytoplasm, cyclic GMP-AMP synthase (cGAS) senses binds virus DNA subsequently activates stimulator interferon genes (STING) to trigger series intracellular signalling cascades defend against invading pathogenic microorganisms. Integrated omic functional analyses identify cGAS-STING pathway regulating various cellular controlling infections. Aside from its most common function inflammation type I interferon, growing body evidence suggests that axis is closely associated responses, such as oxidative stress, autophagy, endoplasmic reticulum which have major impacts on physiological homeostasis. Interestingly, these dual regulation clearance viruses. Here, we outline recent insights into inflammation, autophagy stress discuss their interactions A detailed understanding cGAS-STING-mediated potential antiviral effects contributes revealing pathogenesis certain viruses sheds light effective solutions for therapy.

Language: Английский

Citations

10
The multiple roles of nsp6 in the molecular pathogenesis of SARS-CoV-2 DOI Open Access
Cody J. Bills, Xuping Xie, Pei‐Yong Shi

et al.

Antiviral Research, Journal Year: 2023, Volume and Issue: 213, P. 105590 - 105590

Published: March 31, 2023

Language: Английский

Citations

13
Long COVID: Molecular Mechanisms and Detection Techniques DOI Open Access
Adela Constantinescu‐Bercu, Andrei Lobiuc, Olga Adriana Căliman-Sturdza

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 25(1), P. 408 - 408

Published: Dec. 28, 2023

Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), has emerged a significant health concern following the COVID-19 pandemic. Molecular mechanisms underlying occurrence and progression long COVID include viral persistence, immune dysregulation, endothelial dysfunction, neurological involvement, highlight need for further research to develop targeted therapies this condition. While clearer picture clinical symptomatology is shaping, many molecular are yet be unraveled, given their complexity high level interaction with other metabolic pathways. This review summarizes some most important symptoms associated that occur in well relevant techniques can used understanding pathogen, its affinity towards host, possible outcomes host-pathogen interaction.

Language: Английский

Citations

13
DAZAP2 functions as a pan-coronavirus restriction factor by inhibiting viral entry and genomic replication DOI Creative Commons

Fei Feng,

Jiannan Chen, Rong Li

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 7, 2025

ABSTRACT The SARS-CoV-2 pandemic and the emergence of novel variants underscore need to understand host-virus interactions identify host factors that restrict viral infection. Here, we perform a genome-wide CRISPR knockout screen restriction for SARS-CoV-2, revealing DAZAP2 as potent antiviral gene. DAZAP2, previously implicated in restriction, is found inhibit entry by blocking virion fusion with both endolysosomal plasma membranes. Additionally, suppresses genomic RNA replication without affecting primary translation replicases. We demonstrate functions pan-coronavirus factor across four genera coronaviruses. Importantly, enhances infection mouse models human airway epithelial cells, confirming its physiological relevance. Mechanistically, activity appears be indirect, potentially through regulation gene expression, it primarily localizes nucleus. Our findings provide new insights into defense system against coronaviruses highlight potential target host-directed therapies. IMPORTANCE During infection, response mediated variety distinct mechanisms have yet fully elucidated. Although was action vivo relevance remain unclear. In this study, inhibits dual mechanisms: membranes, suppressing replication. confirm using cell cultures. This study advances our understanding host-pathogen interactions. Targeting or regulatory pathways could approach enhance current future coronavirus threats.

Language: Английский

Citations

0
Host-targeted antivirals against SARS-CoV-2 in clinical development - prospect or disappointment? DOI Creative Commons
André Schreiber, Stephan Ludwig

Antiviral Research, Journal Year: 2025, Volume and Issue: 235, P. 106101 - 106101

Published: Feb. 7, 2025

The global response to the COVID-19 pandemic, caused by novel SARS-CoV-2 virus, has seen an unprecedented increase in development of antiviral therapies. Traditional strategies have primarily focused on direct-acting antivirals (DAAs), which specifically target viral components. In recent years, increasing attention was given alternative approach aiming exploit host cellular pathways or immune responses inhibit replication, led so-called host-targeted (HTAs). emergence and promoted a boost this field. Numerous HTAs been tested demonstrated their potential against through vitro vivo studies. However, striking contrast, only limited number successfully progressed advanced clinical trial phases (2-4), even less entered practice. This review aims explore current landscape targeting that reached phase 2-4 trials. Additionally, it will challenges faced gaining regulatory approval market availability.

Language: Английский

Citations

0
Integrative Multi‐Omics and Routine Blood Analysis Using Deep Learning: Cost‐Effective Early Prediction of Chronic Disease Risks DOI Creative Commons
Zhibin Dong, Pei Li, Yi Jiang

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: April 2, 2025

Chronic noncommunicable diseases (NCDS) are often characterized by gradual onset and slow progression, but the difficulty in early prediction remains a substantial health challenge worldwide. This study aims to explore interconnectedness of disease occurrence through multi-omics studies validate it large-scale electronic records. In response, research examined data from 160 sub-healthy individuals at high altitude then deep learning model called Omicsformer is developed for detailed analysis classification routine blood samples. adeptly identified potential risks nine including cancer, cardiovascular conditions, psychiatric conditions. Analysis risk trajectories 20 years large clinical patients confirmed validity group preclinical assessment, revealing trends increased time onset. Additionally, straightforward NCDs system developed, utilizing basic test results. work highlights role multiomics chronic risk, development validation predictive models based on results can help advance personalized medicine reduce cost screening community.

Language: Английский

Citations

0
SARS-CoV-2 Covid-19 Infection During Pregnancy and Differential DNA Methylation in Human Cord Blood Cells From Term Neonates DOI Creative Commons

Pedro Urday,

Suhita Gayen Betal,

Rochelle Sequeira Gomes

et al.

Epigenetics Insights, Journal Year: 2023, Volume and Issue: 16

Published: Jan. 1, 2023

Background: The global pandemic of coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome 2 (SARS-CoV-2). About 18.4% total Covid-19 cases were reported in children. Even though vertical transmission from mother to infant likely occur at a low rate, exposure COVID-19 during fetal life may alter DNA methylation patterns with potential long-term effects. Objective: To determine if infection pregnancy alters the umbilical cord blood cells term infants and identify pathways genes affected infection. Methods: Umbilical was collected 8 exposed control no exposure. Genomic isolated genome-wide performed using Illumina Methylation EPIC Array. Results: 119 differentially methylated loci identified FDR level 0.20 (64 hypermethylated 55 hypomethylated loci) neonates compared group. Important canonical Ingenuity Pathway Analysis (IPA) related stress response (corticotropin releasing hormone signaling, glucocorticoid receptor oxytocin brain signaling pathway), cardiovascular development (nitric oxide system, apelin cardiomyocyte pathways, factors promoting cardiogenesis, renin-angiotensin signaling). differential methylations associated cardiac, renal, hepatic, neurological diseases, developmental immunological disorders. Conclusions: induces cells. contribute disorders offspring born mothers pregnancy, their regulation.

Language: Английский

Citations

7
Proteomic Analysis Identifies Molecular Players and Biological Processes Specific to SARS-CoV-2 Exposure in Endothelial Cells DOI Open Access
Thatiana Corrêa de Melo, Dilza Trevisan-Silva, Miryam Paola Alvarez‐Flores

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(18), P. 10452 - 10452

Published: Sept. 9, 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for the severe pandemic of disease, disease 2019 (COVID-19), experienced in 21st century. The clinical manifestations range from mild symptoms to abnormal blood coagulation and failure. In cases, COVID-19 manifests as a thromboinflammatory disease. Damage vascular compartment caused by SARS-CoV-2 linked thrombosis, triggered an enhanced immune response. molecular mechanisms underlying endothelial activation have not fully elucidated. We aimed identify proteins correlated response human umbilical vein cells (HUVECs) after exposure SARS-CoV-2, which might help unravel endothelium COVID-19. this direction, we exposed HUVECs analyzed expression specific cellular receptors, changes proteome at different time points. identified that exhibit non-productive infection without cytopathic effects, addition lack cell receptors known be essential entry into cells. highlighted enrichment protein SUMOylation pathway increase SUMO2, was confirmed orthogonal assays. conclusion, proteomic analysis revealed induced oxidative stress abundance pathways resembled dysfunction.

Language: Английский

Citations

10