7HKS
Group deposition for crystallographic fragment screening of the NS5 RNA-dependent RNA polymerase from Dengue virus serotype 2 -- Crystal structure of the NS5 RNA-dependent RNA polymerase from Dengue virus serotype 2 in complex with Z198194394 (DNV2_NS5A-x0612)
Summary for 7HKS
| Entry DOI | 10.2210/pdb7hks/pdb |
| Group deposition | Group deposition for crystallographic fragment screening of the NS5 RNA-dependent RNA polymerase from Dengue virus serotype 2 (G_1002317) |
| Descriptor | Genome polyprotein, ZINC ION, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, ... (8 entities in total) |
| Functional Keywords | diamond light source, rutgers university, i04-1, readdi, dengue virus, crystallographic fragment screening, pandda, xchemexplorer, viral protein |
| Biological source | dengue virus type 2 |
| Total number of polymer chains | 1 |
| Total formula weight | 75075.89 |
| Authors | Saini, M.,Chopra, A.,Aschenbrenner, J.C.,Marples, P.G.,Balcomb, B.H.,Fearon, D.,von Delft, F.,Ruiz, F.X.,Arnold, E. (deposition date: 2024-10-15, release date: 2024-10-30, Last modification date: 2026-06-24) |
| Primary citation | Saini, M.,Aschenbrenner, J.C.,Ruiz, F.X.,Chopra, A.,Chandran, A.V.,Marples, P.G.,Balcomb, B.H.,Fearon, D.,von Delft, F.,Arnold, E. Crystallographic Fragment Screening of the Dengue Virus Polymerase Reveals Multiple Binding Sites for the Development of Non-nucleoside Antiflavivirals. J.Med.Chem., 68:18356-18369, 2025 Cited by PubMed Abstract: Dengue viruses (DENVs) infect approximately 400 million people each year, and currently, there are no effective therapeutics available. To explore potential starting points for antiviral drug development, we conducted a large-scale crystallographic fragment screen targeting the RNA-dependent RNA polymerase (RdRp) domain of the nonstructural protein 5 (NS5) from DENV serotype 2. Our screening, which involved 1108 fragments, identified 60 hit compounds across various known binding sites, including the active site, N pocket, and RNA tunnel. Additionally, we discovered a novel binding site and a fragment-binding hot spot in thumb site II. These structural findings open amenable avenues for developing non-nucleoside inhibitors and offer valuable insights for future structure-based drug design aimed at DENV and other flaviviral RdRps. PubMed: 40892049DOI: 10.1021/acs.jmedchem.5c01014 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.56 Å) |
Structure validation
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