Journal of Molecular Biology, Journal Year: 2023, Volume and Issue: 436(4), P. 168380 - 168380
Published: Dec. 5, 2023
Language: Английский
Molecules, Journal Year: 2023, Volume and Issue: 28(4), P. 1981 - 1981
Published: Feb. 20, 2023
Respiratory viruses represent a world public health problem, giving rise to annual seasonal epidemics and several pandemics caused by some of these viruses, including the COVID-19 pandemic novel SARS-CoV-2, which continues date. Some antiviral drugs have been licensed for treatment influenza, but they cause side effects lead resistant viral strains. Likewise, aerosolized ribavirin is only drug approved therapy infections respiratory syncytial virus, it possesses various limitations. On other hand, no specific are treat diseases. In this sense, natural products their derivatives appeared as promising alternatives in searching new compounds with activity. Besides chemical properties, quinones demonstrated interesting biological activities, activity against viruses. This review summarizes molecular targets different types (both synthetic). Thus, present work offers general overview importance an option future pharmacological infections, subject additional studies that support effectiveness safety.
Language: Английский
Citations
15
Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)
Published: Jan. 24, 2024
Abstract Protein Phosphatase 1 (PP1) is a major serine/threonine phosphatase in eukaryotes, participating several cellular processes and metabolic pathways. Due to their low substrate specificity, PP1’s catalytic subunits do not exist as free entities but instead bind Regulatory Interactors of One (RIPPO), which regulate specificity subcellular localization. Most RIPPOs PP1 through combinations short linear motifs (4–12 residues), forming highly specific holoenzymes. These PP1-binding may, hence, represent attractive targets for the development drugs that interfere with subset Several viruses exploit host cell protein (de)phosphorylation machinery ensure efficient virus particle formation propagation. While role many kinases viral life cycles has been extensively studied, targeting phosphatases by proteins studied less detail. Here, we compile review what known concerning context infections discuss how it may constitute putative host-based target novel antiviral strategies.
Language: Английский
Citations
5
Journal of Biomolecular Structure and Dynamics, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 20
Published: March 7, 2024
The significant mortality rate associated with Marburg virus infection made it the greatest hazard among infectious diseases. Drug repurposing using in silico methods has been crucial identifying potential compounds that could prevent viral replication by targeting virus's primary proteins. This study aimed at drugs of SARS-CoV-2 for candidates against matrix protein VP40 virus. Virtual screening was performed where control compound, Nilotinib, showed a binding score −9.99 kcal/mol. Based on scores, hit 9549298, 11960895, 44545852, 51039094, and 89670174 were selected had lower than control. Subsequent molecular dynamics (MD) simulation revealed compound 9549298 consistently formed hydrogen bond residue Gln290. observed both docking MD poses, indicating strong interaction protein. 11960895 most stable consistent RMSD pattern exhibited 100 ns simulation, while identical plot compared to molecule. MM/PBSA analysis free energy (ΔG) control, −30.84 −38.86 kcal/mol, respectively. It PCA (principal component analysis) FEL (free landscape) lesser conformational variation. Overall, this proposed as binders MARV can cause its inhibition, however inherently lacks experimental validation. Furthermore, proposes in-vitro experiments next step validate these computational findings, offering practical approach further explore compounds' antiviral agents.
Language: Английский
Citations
4
PubMed, Journal Year: 2024, Volume and Issue: 49(3), P. 312 - 318
Published: Feb. 5, 2024
This observational study included all patients undergoing HCV treatment with direct-acting antiviral (DAA)-based therapy between May 2020 and September 2023 at the Dolj County Hospital, Romania. The aim was to investigate adherence DAAs among effect of this on their health-related quality life (HRQoL). Chronic HCV-infected were prospectively evaluated baseline (T0), before beginning treatment, 12 weeks after completing (T1). HCV-AD10 questionnaire used measure adherence, HRQoL assessed 15D instrument. administered two time points: T0 T1, during which Sustained Virologic Response (SVR) also measured. primary outcome secondary outcomes including (QoL), sustained virologic response (SVR). based initiated for 368 patients, whom health insured. psychological state clinically improved. very good (mean±SD, 91.51±8.34), being influenced by age (younger much adherent, rho=-0.112, p-value=0.031) severity disease (patients more severe hepatitis less rho=-0.167, p-value=0.001). had a significant improving but did not influence medication adherence.
Language: Английский
Citations
4
Frontiers in Virology, Journal Year: 2022, Volume and Issue: 2
Published: Aug. 4, 2022
Arboviruses have the potential to spread quickly and cause a global health emergency. These are RNA viruses that use RNA-dependent polymerase (RdRp) for their replication. RdRp lacks proofreading activity, leading high error rates, low replicative fidelity, more genetic variability. In addition, shorter generation time faster evolutionary rate of these lead re-emergence recurrence arboviral infections due emergence new variants development antiviral resistance. During replication inside host cell through protein-protein interactions (PPIs), interact with several factors utilize cellular machinery benefit. Besides this, employ transmission strategies combat innate adaptive immune responses by manipulating signaling metabolic pathways hosts. Hence, therapies targeting host-virus PPIs can provide an alternative broad-spectrum strategy against viruses. The approach virus-specific proteins developing antivirals is expected solve problem drug resistance emerging This review focuses on directly affect pathways. Better understanding mechanisms will develop therapeutic tools treat viral infections.
Language: Английский
Citations
19
Pesticide Biochemistry and Physiology, Journal Year: 2025, Volume and Issue: 208, P. 106303 - 106303
Published: Jan. 16, 2025
Language: Английский
Citations
0
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
AAPS PharmSciTech, Journal Year: 2025, Volume and Issue: 26(3)
Published: March 4, 2025
Language: Английский
Citations
0
Viruses, Journal Year: 2025, Volume and Issue: 17(3), P. 390 - 390
Published: March 10, 2025
Chronic viral infections like HIV, HBV, and HCV establish persistent interactions with the host immune system, resulting in evasion long-term dysfunction. These viruses use a range of strategies to limit defenses, such as downregulating MHC class I, disrupting interferon signaling, altering apoptosis pathways, suppressing cytotoxic T-cell activity. Key proteins, including HIV Nef, HBV X protein, NS5A, interfere antigen presentation JAK/STAT thereby reducing antiviral responses. induce exhaustion due exposure, which leads expression inhibitory receptors PD-1 CTLA-4 on T cells. Viral epigenetic changes, N6-methyladenosine modifications histone deacetylation, enhance by modulating gene infected Viruses further manipulate cytokine networks promoting an immunosuppressive environment through IL-10 TGF-β secretion, suppress inflammatory responses inhibit activation. This review examines molecular/cellular mechanisms that enable chronic escape immunity, focusing antigenic variation, disruption, control apoptotic pathways. It also addresses how genetic factors, HLA polymorphisms, influence disease progression. Lastly, we discuss host-targeted therapies, checkpoint inhibitors, treatments, CRISPR.
Language: Английский
Citations
0
Viruses, Journal Year: 2025, Volume and Issue: 17(3), P. 417 - 417
Published: March 14, 2025
Structural virology has emerged as the foundation for development of effective antiviral therapeutics. It is pivotal in providing crucial insights into three-dimensional frame viruses and viral proteins at atomic-level or near-atomic-level resolution. Structure-based assessment components, including capsids, envelope proteins, replication machinery, host interaction interfaces, instrumental unraveling multiplex mechanisms infection, replication, pathogenesis. The structural elucidation enzymes, proteases, polymerases, integrases, been essential combating like HIV-1 HIV-2, SARS-CoV-2, influenza. Techniques X-ray crystallography, Nuclear Magnetic Resonance spectroscopy, Cryo-electron Microscopy, Tomography have revolutionized field significantly aided discovery ubiquity chronic infections, along with emergence reemergence new threats necessitate novel strategies agents, while extensive diversity their high mutation rates further underscore critical need analysis to aid development. This review highlights significance structure-based investigations bridging gap between structure function, thus facilitating therapeutics, vaccines, antibodies tackling emerging threats.
Language: Английский
Citations
0