Trends in Microbiology, Journal Year: 2024, Volume and Issue: unknown
Published: Dec. 1, 2024
Language: Английский
PLoS Pathogens, Journal Year: 2025, Volume and Issue: 21(1), P. e1012859 - e1012859
Published: Jan. 13, 2025
Chikungunya virus (CHIKV) is an arthritogenic alphavirus that has re-emerged to cause large outbreaks of human infections worldwide. There are currently no approved antivirals for treatment CHIKV infection. Recently, we reported the ribonucleoside analog 4'-fluorouridine (4'-FlU) a highly potent inhibitor replication, and targets viral nsP4 RNA dependent polymerase. In mouse models, oral therapy with 4'-FlU diminished tissue burdens virus-induced disease signs. To provide critical evidence potential as antiviral, here selected variants decreased sensitivity, identifying two pairs mutations in nsP2 nsP4. The Q192L C483Y were predominantly responsible reduced sensitivity. These still inhibited by higher concentrations 4'-FlU, did not change fidelity or fitness advantage vitro vivo. Pathogenesis studies mice showed nsP4-C483Y variant caused similar burden WT CHIKV, while nsP4-Q192L was strongly attenuated. Together these results support be important antiviral against CHIKV.
Language: Английский
Citations
1
Virulence, Journal Year: 2024, Volume and Issue: 15(1)
Published: May 26, 2024
O'nyong-nyong virus (ONNV) is a neglected mosquito-borne alphavirus belonging to the Togaviridae family. ONNV known be responsible for sporadic outbreaks of acute febrile disease and polyarthralgia in Africa. As climate change increases geographical range potential new vectors, recent data indicate possibility spread outside African continent grow into greater public health concern. In this review, we summarise current knowledge on epidemiology, host-pathogen interactions, vector-virus responses, insights possible avenues control risk further epidemics. limited literature compared correlated other findings mainly Old World alphaviruses. We highlight discuss studies that investigate viral host factors determine viral-vector specificity, along with important mechanisms severity outcome infection.
Language: Английский
Citations
4
Reviews in Medical Virology, Journal Year: 2025, Volume and Issue: 35(2)
Published: March 1, 2025
Alphaviruses are re-emerging vector-born pathogens that cause arthralgia or encephalitic diseases on a global scale. While vaccine against chikungunya virus was recently approved, no vaccines currently exist for other alphaviruses, nor there antiviral drugs the treatment of alphavirus infections. have positive-strand RNA genomes, and their replication is coordinated by activities multifunctional nonstructural protein 2 (nsP2), helicase-protease subunit viral replicase. We provide comprehensive overview nsP2 functions inhibitors its potential as effective antivirals. Furthermore, analysis suggests it could be targeted to develop advanced live attenuated strategies controlling transmission mosquito vectors.
Language: Английский
Citations
0
Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16
Published: March 14, 2025
Certain insect-specific viruses (ISVs), specifically the mosquito alphaviruses, Eilat and Yada viruses, orthoflaviviruses, Binjari, Aripo, YN15-283-02 Chaoyang have emerged as potential platforms for generation of whole virus vaccines human veterinary applications. These ISVs are remarkably tolerant substitution their structural polyproteins with those alphaviruses orthoflaviviruses that pathogenic in humans and/or animals. The resulting ISV-based chimeric been evaluated mouse models demonstrated safety efficacy non-human primates, crocodiles pigs. Targets include chikungunya, Venezuelan eastern equine encephalitis, dengue, Zika, yellow fever, Japanese encephalitis West Nile viruses. provide authentically folded tertiary quaternary virion particle structures to immune system, a key feature induction protective antibody responses. manufactured C6/36 or C7-10 cell lines, where they grow high titers, but do not replicate vertebrate vaccine recipients. This review discusses progress these emerging technologies addresses challenges related adjuvanting, safety, manufacturing.
Language: Английский
Citations
0
Archives of Virology, Journal Year: 2025, Volume and Issue: 170(7)
Published: May 27, 2025
Language: Английский
Citations
0
International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 282, P. 137254 - 137254
Published: Nov. 6, 2024
Language: Английский
Citations
2
Acta Biochimica et Biophysica Sinica, Journal Year: 2024, Volume and Issue: 56(10), P. 1425 - 1436
Published: May 29, 2024
Chikungunya virus (CHIKV) is a neglected arthropod-borne and anthropogenic alphavirus. Over the past two decades, CHIKV distribution has undergone significant changes worldwide, from original tropics subtropics regions to temperate regions, which attracted global attention. However, interactions between its host remain insufficiently understood, dampens need for development of an anti-CHIKV strategy. In this study, on basis optimal overexpression non-structural protein 4 (nsP4), we explore nsP4 using mass spectrometry-based protein-protein interaction approaches. The results reveal that some cellular proteins interact with are enriched in ubiquitin-proteasome pathway. Specifically, scaffold receptor activated C kinase 1 (RACK1) identified as novel interactor regulator nsP4. inhibition RACK1 by harringtonolide reduction nsP4, caused promotion degradation but not translation. Furthermore, decrease triggered inhibitor can be reversed proteasome MG132, suggesting protect through This study reveals mechanism factor regulates could potential target developing drugs against CHIKV.
Language: Английский
Citations
0
Viruses, Journal Year: 2024, Volume and Issue: 16(11), P. 1727 - 1727
Published: Oct. 31, 2024
Many vector-borne viruses are re-emerging as public health threats, yet our understanding of the virus-host interactions critical for productive infection remains limited. The ubiquitination proteins, including host- and pathogen-derived proteins is a highly prominent consistent post-translational modification that regulates protein function through signaling degradation. Viral documented to hijack host machinery modulate multiple processes antiviral defense mechanisms. engagement in viral support aspects life cycle assembly egress also well documented. Exploring role plays vector-transmitted pathogens will increase knowledge base pertinent impact host-enabled consequences on pathogenesis. In this review, we explore E3 ligase-regulated pathways functioning proviral restriction factors context acutely infectious, potential therapeutically targeting them countermeasures development.
Language: Английский
Citations
0
Viruses, Journal Year: 2024, Volume and Issue: 16(11), P. 1776 - 1776
Published: Nov. 14, 2024
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza, and syncytial virus (RSV) are significant global health threats. The need for low-cost, easily synthesized oral drugs rapid deployment during outbreaks is crucial. Broad-spectrum therapeutics, or pan-antivirals, designed to target multiple viral pathogens simultaneously by focusing on shared molecular features, such as common metal cofactors conserved residues in catalytic domains. This study introduces a new generation of potent sartans, known bisartans, engineered our laboratories with negative charges from carboxylate tetrazolate groups. These anionic tetrazoles interact strongly cationic arginine cations (e.g., Zn2+) within host sites, including the SARS-CoV-2 ACE2 receptor, influenza H1N1 neuraminidases, RSV fusion protein. Using virtual ligand docking dynamics, we investigated how bisartans their analogs bind these receptors, potentially blocking infection through pan-antiviral mechanism. Bisartan, ACC519TT, demonstrated stable high-affinity key domains NSP3, neuraminidase, protein, outperforming FDA-approved like Paxlovid oseltamivir. It also showed strong binding arginine-rich furin cleavage sites S1/S2 S2′, suggesting interference SARS-CoV-2’s spike protein cleavage. results highlight potential tetrazole-based promising candidates developing broad-spectrum antiviral therapies.
Language: Английский
Citations
0
Trends in Microbiology, Journal Year: 2024, Volume and Issue: unknown
Published: Dec. 1, 2024
Language: Английский
Citations
0