ArticleCommunications biology2024
A conformational selection mechanism of flavivirus NS5 for species-specific STAT2 inhibition.
Article in Communications biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 15 citations in OpenAlex.
- Dengue Virus NS5 Target Discovery: A Comprehensive in Silico Exploration of Novel Druggable Sites for Pan-Serotype Antiviral Design.International journal of molecular sciences · 2026Article
- A non-canonical JAK/STAT pathway promotes viral replication through the lipoprotein receptor-related protein in ticks.PLoS biology · 2026Article
- Japanese encephalitis virus degrades TRAF3 to suppress type I interferon and promote viral replication through NS5 and host TUFM proteins.Veterinary research · 2026Article
- Integrative proteome-wide structural analysis and high-throughput docking identify broad-spectrum antiviral scaffolds against Zika, Yellow Fever, West Nile, Saint Louis encephalitis, and Usutu viruses.Frontiers in cellular and infection microbiology · 2026Article
- Targeting dengue through mucosal vaccination: the potential of NS1 and bacterial spore-based delivery platforms.Frontiers in immunology · 2026Review
- Phosphorylation landscape of dengue virus proteins and their implications in protein-protein interactions.PloS one · 2026Article
- Coevolutionary constraints of Zika virus nonstructural protein 5 replication and interferon antagonism activities.bioRxiv : the preprint server for biology · 2025Article
- Interaction of West Nile virus NS5 with orthoflavivirus SLA RNAs and their effects on viral replication and inhibition.Journal of virology · 2025Article
- Crystallographic Fragment Screening of the Dengue Virus Polymerase Reveals Multiple Binding Sites for the Development of Non-nucleoside Antiflavivirals.Journal of medicinal chemistry · 2025Article
- MARCH6 suppresses Tembusu virus replication by targeting viral NS5 protein for TOLLIP-mediated selective autophagic degradation.Journal of virology · 2025Article
- Structural dynamics of the dengue virus non-structural 5 (NS5) interactions with promoter stem-loop A (SLA).Npj viruses · 2025Article
- Identification of Benzothiophene-Derived Inhibitors of Flaviviruses by Targeting RNA-Dependent RNA Polymerase.Viruses · 2025Article
- Article
- Animal Models, Therapeutics, and Vaccine Approaches to Emerging and Re-Emerging Flaviviruses.Viruses · 2024Review
- Etravirine Prevents West Nile Virus and Chikungunya Virus Infection Both In Vitro and In Vivo by Inhibiting Viral Replication.Pharmaceutics · 2024Article
- Zika virus NS5 protein inhibits type I interferon signaling via CRL3 E3 ubiquitin ligase-mediated degradation of STAT2.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The Flavivirus Non-Structural Protein 5 (NS5): Structure, Functions, and Targeting for Development of Vaccines and Therapeutics.Vaccines · 2024Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Flaviviruses, including Zika virus (ZIKV) and Dengue virus (DENV), rely on their non-structural protein 5 (NS5) for both replication of viral genome and suppression of host IFN signaling. DENV and ZIKV NS5s were shown to facilitate proteosome-mediated protein degradation of human STAT2 (hSTAT2). However, how flavivirus NS5s have evolved for species-specific IFN-suppression remains unclear. Here we report structure-function characterization of the DENV serotype 2 (DENV2) NS5-hSTAT2 complex. The MTase and RdRP domains of DENV2 NS5 form an extended conformation to interact with the coiled-coil and N-terminal domains of hSTAT2, thereby promoting hSTAT2 degradation in cells. Disruption of the extended conformation of DENV2/ZIKV NS5, but not the alternative compact state, impaired their hSTAT2 binding. Our comparative structural analysis of flavivirus NS5s further reveals a conserved protein-interaction platform with subtle amino-acid variations likely underpinning diverse IFN-suppression mechanisms. Together, this study uncovers a conformational selection mechanism underlying species-specific hSTAT2 inhibition by flavivirus NS5.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.