SARS-CoV-2 and the DNA damage response DOI
Roger J.A. Grand

Journal of General Virology, Journal Year: 2023, Volume and Issue: 104(11)

Published: Nov. 10, 2023

The recent coronavirus disease 2019 (COVID-19) pandemic was caused by severe acute respiratory syndrome 2 (SARS-CoV-2). COVID-19 is characterized distress, multiorgan dysfunction and, in some cases, death. virus also responsible for post-COVID-19 condition (commonly referred to as ‘long COVID’). SARS-CoV-2 a single-stranded, positive-sense RNA with genome of approximately 30 kb, which encodes 26 proteins. It has been reported affect multiple pathways infected cells, resulting, many the induction ‘cytokine storm’ and cellular senescence. Perhaps because it an virus, replicating largely cytoplasm, effect SARS-Cov-2 on stability DNA damage responses (DDRs) received relatively little attention. However, now becoming clear that causes DNA, shown presence micronuclei, repair foci increased comet tails cells. This review considers evidence indicating how instability, deregulates cell cycle targets specific components DDR pathways. significance virus’s ability cause senescence considered, are implications instability patients suffering from long COVID.

Language: Английский

NF-κB in biology and targeted therapy: new insights and translational implications DOI Creative Commons
Qing Guo, Yizi Jin, Xinyu Chen

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: March 4, 2024

Abstract NF-κB signaling has been discovered for nearly 40 years. Initially, was identified as a pivotal pathway in mediating inflammatory responses. However, with extensive and in-depth investigations, researchers have that its role can be expanded to variety of mechanisms, biological processes, human diseases, treatment options. In this review, we first scrutinize the research process signaling, summarize composition, activation, regulatory mechanism signaling. We investigate interaction other important pathways, including PI3K/AKT, MAPK, JAK-STAT, TGF-β, Wnt, Notch, Hedgehog, TLR The physiological pathological states well intricate involvement inflammation, immune regulation, tumor microenvironment, are also explicated. Additionally, illustrate how is involved cancers, autoimmune cardiovascular metabolic neurological COVID-19. Further, discuss therapeutic approaches targeting IKK inhibitors, monoclonal antibodies, proteasome nuclear translocation DNA binding TKIs, non-coding RNAs, immunotherapy, CAR-T. Finally, provide an outlook field hope present stereoscopic, comprehensive will inform future clinical practice.

Language: Английский

Citations

451
SARS-CoV-2 reservoir in post-acute sequelae of COVID-19 (PASC) DOI Open Access
Amy D. Proal, Michael B. VanElzakker, Soo Aleman

et al.

Nature Immunology, Journal Year: 2023, Volume and Issue: 24(10), P. 1616 - 1627

Published: Sept. 4, 2023

Language: Английский

Citations

186
Immunomodulatory Role of Interferons in Viral and Bacterial Infections DOI Open Access
Paulina Mertowska,

Konrad Smolak,

Sebastian Mertowski

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(12), P. 10115 - 10115

Published: June 14, 2023

Interferons are a group of immunomodulatory substances produced by the human immune system in response to presence pathogens, especially during viral and bacterial infections. Their remarkably diverse mechanisms action help fight infections activating hundreds genes involved signal transduction pathways. In this review, we focus on discussing interplay between IFN seven medically important challenging viruses (herpes simplex virus (HSV), influenza, hepatitis C (HCV), lymphocytic choriomeningitis (LCMV), immunodeficiency (HIV), Epstein–Barr (EBV), SARS-CoV coronavirus) highlight diversity strategies. addition, available data also suggest that IFNs play an role course Research is currently underway identify elucidate exact specific effector pathways generating antimicrobial mediated IFNs. Despite numerous studies interferons responses, many interdisciplinary still needed understand optimize their use personalized therapeutics.

Language: Английский

Citations

52
Deucravacitinib in plaque psoriasis: 2-year safety and efficacy results from the phase III POETYK trials DOI Creative Commons
Mark Lebwohl, Richard B. Warren, Howard Sofen

et al.

British Journal of Dermatology, Journal Year: 2024, Volume and Issue: 190(5), P. 668 - 679

Published: Jan. 16, 2024

In the phase III POETYK PSO-1 and PSO-2 trials, deucravacitinib, an oral selective allosteric tyrosine kinase 2 inhibitor, was well tolerated efficacious over 1 year in patients with psoriasis.

Language: Английский

Citations

28
Evolution of the SARS-CoV-2 Omicron Variants: Genetic Impact on Viral Fitness DOI Creative Commons
Wenhao Liu, Zehong Huang, Jin Xiao

et al.

Viruses, Journal Year: 2024, Volume and Issue: 16(2), P. 184 - 184

Published: Jan. 25, 2024

Over the last three years, pandemic of COVID-19 has had a significant impact on people’s lives and global economy. The incessant emergence variant strains compounded challenges associated with management COVID-19. As predominant from late 2021 to present, Omicron its sublineages, through continuous evolution, have demonstrated iterative viral fitness. comprehensive elucidation biological implications that catalyzed this evolution remains incomplete. In accordance extant research evidence, we provide review subvariants Omicron, delineating alterations in immune evasion, cellular infectivity, cross-species transmission potential. This seeks clarify underpinnings biology within SARS-CoV-2, thereby providing foundation for strategic considerations post-pandemic era

Language: Английский

Citations

26
The multiple roles of interferon regulatory factor family in health and disease DOI Creative Commons

Luyao Wang,

Yanghui Zhu,

Nan Zhang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Oct. 9, 2024

Interferon Regulatory Factors (IRFs), a family of transcription factors, profoundly influence the immune system, impacting both physiological and pathological processes. This review explores diverse functions nine mammalian IRF members, each featuring conserved domains essential for interactions with other factors cofactors. These allow IRFs to modulate broad spectrum processes, encompassing host defense, response, cell development. Conversely, their pivotal role in regulation implicates them pathophysiology various diseases, such as infectious autoimmune disorders, metabolic cancers. In this context, display dichotomous nature, functioning tumor suppressors promoters, contingent upon specific disease milieu. Post-translational modifications IRFs, including phosphorylation ubiquitination, play crucial modulating function, stability, activation. As prospective biomarkers therapeutic targets, present promising opportunities intervention. Further research is needed elucidate precise mechanisms governing regulation, potentially pioneering innovative strategies, particularly cancer treatment, where equilibrium activities paramount importance.

Language: Английский

Citations

15
Induction of the Inflammasome by the SARS‐CoV‐2 Accessory Protein ORF9b, Abrogated by Small‐Molecule ORF9b Homodimerization Inhibitors DOI
Erika Zodda, Mònica Pons, Natàlia DeMoya‐Valenzuela

et al.

Journal of Medical Virology, Journal Year: 2025, Volume and Issue: 97(2)

Published: Feb. 1, 2025

ABSTRACT Viral accessory proteins play critical roles in viral escape from host innate immune responses and inflammatory pathogenesis. Here we show that the SARS‐CoV‐2 protein, ORF9b, but not other (ORF3a, ORF3b, ORF6, ORF7, ORF8, ORF9c, ORF10), strongly activates inflammasome‐dependent caspase‐1 A549 lung carcinoma cells THP‐1 monocyte‐macrophage cells. Exposure to lipopolysaccharide (LPS) ATP additively enhanced activation of by suggesting ORF9b LPS follow parallel pathways inflammasome caspase‐1. Following rational silico approaches, have designed small molecules capable inhibiting homodimerization which experimentally inhibited ORF9b‐ORF9b homotypic interactions, caused mitochondrial eviction ORF9b‐induced cells, cytokine release restored type I interferon (IFN‐I) signaling suppressed both cell models. These are first‐in‐class compounds targeting a protein for viral‐induced exacerbated inflammation responses, with potential mitigating severe immunopathogenic damage induced highly pathogenic coronaviruses restoring antiviral curtailed infection.

Language: Английский

Citations

1
Plant and animal positive-sense single-stranded RNA viruses encode small proteins important for viral infection in their negative-sense strand DOI Creative Commons
Pan Gong, Qingtang Shen, Mingzhen Zhang

et al.

Molecular Plant, Journal Year: 2023, Volume and Issue: 16(11), P. 1794 - 1810

Published: Sept. 29, 2023

Language: Английский

Citations

18
Role of interferons in the antiviral battle: from virus-host crosstalk to prophylactic and therapeutic potential in SARS-CoV-2 infection DOI Creative Commons

Grigore Mihăescu,

Mariana Carmen Chifiriuc, Roxana Filip

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 15, 2024

Mammalians sense antigenic messages from infectious agents that penetrate the respiratory and digestive epithelium, as well signals damaged host cells through membrane cytosolic receptors. The transduction of these triggers a personalized response, depending on nature stimulus host’s genetics, physiological condition, comorbidities. Interferons (IFNs) are primary effectors innate immune their synthesis is activated in most within few hours after pathogen invasion. IFNs primarily synthesized infected cells, but anti-infective effect extended to neighboring by autocrine paracrine action. emergence severe acute syndrome coronavirus 2 (SARS‐CoV‐2) pandemic 2019 was stark reminder potential threat posed newly emerging viruses. This has also triggered an overwhelming influx research studies aiming unveil mechanisms protective versus pathogenic responses induced SARS‐CoV‐2. purpose this review describe role vital players battle against SARS‐CoV-2 infection. We will briefly characterize classify IFNs, present inductors IFN synthesis, sensors, signaling pathways, then discuss controlling evolution SARS-CoV-2 infection its clinical outcome. Finally, we perspectives controversies regarding prophylactic therapeutic

Language: Английский

Citations

8
Comparative Review of the State of the Art in Research on the Porcine Epidemic Diarrhea Virus and SARS-CoV-2, Scope of Knowledge between Coronaviruses DOI Creative Commons
Nora Hilda Rosas-Murrieta,

Alan Rodríguez-Enríquez,

Irma Herrera‐Camacho

et al.

Viruses, Journal Year: 2024, Volume and Issue: 16(2), P. 238 - 238

Published: Feb. 2, 2024

This review presents comparative information corresponding to the progress in knowledge of some aspects infection by porcine epidemic diarrhea virus (PEDV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) coronaviruses. PEDV is an alphacoronavirus great economic importance due million-dollar losses it generates pig industry. has many similarities SARS-CoV-2 betacoronavirus that causes COVID-19 disease. possible scenarios for based on collected literature tools or strategies currently developed would be useful research. The speed study generation control pandemic was derived from infections caused other human coronaviruses such as (SARS) middle east (MERS). Therefore, obtained several coronaviruses, current future behavior could inferred and, with large amount COVID-19, improved probably new emerging re-emerging

Language: Английский

Citations

7