8JIX
Crystal structure of the Bagaza virus helicase and structure-based discovery of a novel inhibitor
Summary for 8JIX
| Entry DOI | 10.2210/pdb8jix/pdb |
| Descriptor | Genome polyprotein (2 entities in total) |
| Functional Keywords | ns3 helicase, epigallocatechin-3-gallate, molecular docking, structural protein |
| Biological source | Bagaza virus |
| Total number of polymer chains | 1 |
| Total formula weight | 49406.20 |
| Authors | Zhao, R.,Shu, W.,Cao, J.M.,Zhou, X.,Wang, D.P. (deposition date: 2023-05-29, release date: 2024-03-06, Last modification date: 2025-05-28) |
| Primary citation | Zhao, R.,Shu, W.,Hu, W.S.,Chen, C.,Ning, J.Y.,Luo, J.,Bai, S.P.,Cao, J.M.,Zhou, X.,Wang, D.P. Structure-based discovery of dual-target inhibitors of the helicase from bagaza virus. Int.J.Biol.Macromol., 294:139536-139536, 2025 Cited by PubMed Abstract: Bagaza virus (BAGV) is a mosquito-borne flavivirus and has caused significant avian death in many regions, and also garnered recognition as a significant human pathogen causing diseases like encephalitis. The genome of BAGV encodes ten proteins including three structural proteins and seven nonstructural proteins. The C-terminus of the BAGV NS3 helicase serves as a helicase during BAGV replication, aiding in ATP hydrolysis and unwinding of double-stranded RNA. Here we determined the crystal structure of BAGV helicase and revealed the NTP and RNA binding pockets in the helicase which may be used for exploiting antiviral therapeutics. Using structure-based virtual screening, we discovered 20 compounds targeting both NTP and RNA binding pockets of the helicase. Molecular docking, mutation analysis, isothermal calorimetry (ITC) and the ATPase activity assay demonstrated that epigallocatechin-3-gallate (EGCG), and other top three screened compounds (Quercitrin, Citicoline sodium, Isochlorogenic acid C), showed binding affinities for both the NTP binding site and the RNA binding site of BAGV helicase, and inhibited the ATPase activity of the helicase. Taken together, our discovery of dual-target inhibitors provides a viable strategy for advancing innovative therapies against BAGV, as well as other flaviviruses. PubMed: 39765299DOI: 10.1016/j.ijbiomac.2025.139536 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.71 Å) |
Structure validation
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