Orthoflavivirus infection and the mTOR signaling pathway

Frontiers in Microbiology, Journal Year: 2025, Volume and Issue: 16

Published: April 9, 2025

Each year, mosquito-borne orthoflaviviruses, including Zika virus, dengue and the Japanese encephalitis threaten health of more than 400 million people worldwide. To date, knowledge about pathogenic mechanisms underlying orthoflavivirus infection interactions these viruses with host cells is limited. Mammalian target rapamycin (mTOR) pivotal for cell growth metabolism. The downstream targets mTOR regulate protein translation autophagy to affect replication, its upstream AKT performs similar functions. In this work, mechanism relationship between signaling pathway was reviewed from three perspectives: structure life cycle, pathway, regulation during infection.

Language: Английский

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Design, Synthesis, and Biological Evaluation of Novel Coumarin Analogs Targeted against SARS-CoV-2

Molecules, Journal Year: 2024, Volume and Issue: 29(6), P. 1406 - 1406

Published: March 21, 2024

SARS-CoV, an RNA virus, is contagious and displays a remarkable degree of adaptability, resulting in intricate disease presentations marked by frequent genetic mutations that can ultimately give rise to drug resistance. Targeting its viral replication cycle could be potential therapeutic option counter growth the human body leading severe infectious stage. The Mpro SARS-CoV-2 promising target for development as it crucial transcription replication. derivatives β-diketone coumarin have already been reported their antiviral and, thus, are considered scaffold current study computational design analogs targeting SARS-CoV-2. In our study, we used novel diketone-hinged against MPro develop broad-spectrum agent Through analysis pharmacokinetics docking studies, identified list top 10 compounds demonstrated effectiveness inhibiting virus. On basis analyses, 5 were synthesized characterized. thermodynamic stability KS82 KS94 was confirmed molecular dynamics, simulated system indicated inhibitory nature. Molecules further evaluated anti-viral using Vero E6 cells followed RT-PCR assay test compound most active with inhibit cells. These data indicate prevents attack virus emerges primary candidate properties.

Language: Английский

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Activation of neurotoxic A1‐reactive astrocytes by SFTS virus infection accelerates fatal brain damage in IFNAR1^‐/‐ mice

Journal of Medical Virology, Journal Year: 2024, Volume and Issue: 96(8)

Published: Aug. 1, 2024

Severe fever with thrombocytopenia syndrome (SFTS) has a high mortality rate compared to other infectious diseases. SFTS is particularly associated risk of in immunocompromised individuals, while most patients who die exhibit symptoms severe encephalitis before death. However, the region brain damage and mechanisms by which virus (SFTSV) causes remains unknown. Here, we revealed that SFTSV infects brainstem spinal cord, are regions respiratory function, motor nerves IFNAR1

Language: Английский

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Role of RNA G-Quadruplexes in the Japanese Encephalitis Virus Genome and Their Recognition as Prospective Antiviral Targets

ACS Infectious Diseases, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 22, 2024

G-quadruplexes (GQs) have been primarily studied in the context of cancer and neurodegenerative pathologies. However, recent research has shifted focus to their existence functional roles viral genomes, revealing GQ-regulated key pathways various human pathogenic viruses. While GQ structures reported genomes emerging re-emerging viruses, RNA viruses understudied compared DNA including notable examples such as immunodeficiency virus-1, hepatitis C virus, Ebola Nipah Zika SARS-CoV-2. The flavivirus family, comprising Japanese encephalitis virus (JEV), poses a significant global threat due recurring outbreaks yet lacks approved antivirals. In this study, we identified characterized eight putative G-quadruplex-forming motifs within essential genes involved genome replication, assembly, internalization host cell, conserved across different JEV isolates. formation stability these were validated through multitude biophysical cell-based assays. interaction binding affinity with known GQ-binding ligand BRACO-19 supported by assays, confirming capability form structures. Notably, also exerted antiviral properties reduction replication infectious titers well inhibition protein expression, evaluated This comprehensive molecular characterization G-quadruplex highlights potential promising targets for intervention strategies against infection GQ-specific ligands.

Language: Английский

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The modulation of proteomics and antioxidant stress is involved in the effect of nitazoxanide against Japanese encephalitis virus in vitro

Veterinary Microbiology, Journal Year: 2024, Volume and Issue: 298, P. 110289 - 110289

Published: Oct. 24, 2024

Language: Английский

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