ArticleThe Journal of biological chemistry2011
Functional analysis of two cavities in flavivirus NS5 polymerase.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed.
- In Silico and in vitro antiviral activity of FDA approved drugs from ZINC database against RNA-dependent RNA polymerase of dengue virus.Virology journal · 2026Article
- Structural dynamics of the dengue virus non-structural 5 (NS5) interactions with promoter stem-loop A (SLA).Npj viruses · 2025Article
- The interaction of Orthoflavivirus nonstructural proteins 3 and 5 with human fatty acid synthase.PloS one · 2025Article
- New dengue virus inhibitors targeting NS3-NS5 interaction identified byFrontiers in microbiology · 2025Article
- Repurposing of approved antivirals against dengue virus serotypes: an in silico and in vitro mechanistic study.Molecular diversity · 2024Article
- Residue K28 of Zika Virus NS5 Protein Is Implicated in Virus Replication and Antagonism of STAT2.Microorganisms · 2024Article
- Deciphering the interaction surface between the West Nile virus NS3 and NS5 proteins.Access microbiology · 2024Article
- Review
- Small-Molecule Inhibitor of Flaviviral NS3-NS5 Interaction with Broad-Spectrum Activity and EfficacymBio · 2023Article
- Review
- A conserved arginine in NS5 binds genomic 3' stem-loop RNA for primer-independent initiation of flavivirus RNA replication.RNA (New York, N.Y.) · 2022Article
- Innate and adaptive immune evasion by dengue virus.Frontiers in cellular and infection microbiology · 2022Review
- Dengue virus NS4B protein as a target for developing antivirals.Frontiers in cellular and infection microbiology · 2022Review
- Virtual Screening of Drug-Like Compounds as Potential Inhibitors of the Dengue Virus NS5 Protein.Frontiers in chemistry · 2022Article
- System-oriented optimization of multi-target 2,6-diaminopurine derivatives: Easily accessible broad-spectrum antivirals active against flaviviruses, influenza virus and SARS-CoV-2.European journal of medicinal chemistry · 2021Article
- Article
- Current Trends and Limitations in Dengue Antiviral Research.Tropical medicine and infectious disease · 2021Review
- Structure and Dynamics of Zika Virus Protease and Its Insights into Inhibitor Design.Biomedicines · 2021Review
- Compartmentalized replication organelle of flavivirus at the ER and the factors involved.Cellular and molecular life sciences : CMLS · 2021Review
- Review
12 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Flavivirus NS5 protein encodes methyltransferase and RNA-dependent RNA polymerase (RdRp) activities. Structural analysis of flavivirus RdRp domains uncovered two conserved cavities (A and B). Both cavities are located in the thumb subdomains and represent potential targets for development of allosteric inhibitors. In this study, we used dengue virus as a model to analyze the function of the two RdRp cavities. Amino acids from both cavities were subjected to mutagenesis analysis in the context of genome-length RNA and recombinant NS5 protein; residues critical for viral replication were subjected to revertant analysis. For cavity A, we found that only one (Lys-756) of the seven selected amino acids is critical for viral replication. Alanine substitution of Lys-756 did not affect the RdRp activity, suggesting that this residue functions through a nonenzymatic mechanism. For cavity B, all four selected amino acids (Leu-328, Lys-330, Trp-859, and Ile-863) are critical for viral replication. Biochemical and revertant analyses showed that three of the four mutated residues (Leu-328, Trp-859, and Ile-863) function at the step of initiation of RNA synthesis, whereas the fourth residue (Lys-330) functions by interacting with the viral NS3 helicase domain. Collectively, our results have provided direct evidence for the hypothesis that cavity B, but not cavity A, from dengue virus NS5 polymerase could be a target for rational drug design.
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