EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Differential inhibition of Morbillivirus and Henipavirus polymerases by ERDRP-0519 and structure-guided inhibitor optimization.
ジャーナル・号・ページ	Cell, Vol. 189, Issue 13, Page 4094-4106.e13, Year 2026
掲載日	2026年6月25日
著者	Lu Xue / Jiacheng Gui / Shenghua Gao / Xiaoxiao Gao / Tiancai Chang / Hainei Pan / Jielin Tang / Mingxia Zhang / Zimu Li / Binqian Zou / Heyu Zhao / Longyu Wang / Mei Li / Lijun Rong / Richard K Plemper / Xinwen Chen / Jun He / Rongjuan Pei / Peng Zhan / Xiaoli Xiong /
PubMed 要旨	ERDRP-0519 is a non-nucleoside polymerase inhibitor developed against measles virus (MeV) of the Morbillivirus genus. Here, we show that ERDRP-0519 also cross-inhibits Nipah virus (NiV) of the ...ERDRP-0519 is a non-nucleoside polymerase inhibitor developed against measles virus (MeV) of the Morbillivirus genus. Here, we show that ERDRP-0519 also cross-inhibits Nipah virus (NiV) of the Henipavirus genus with reduced potency. ERDRP-0519 binds to a shared pocket within the RNA-dependent RNA polymerase (RdRp) palm domains of MeV, peste des petits ruminants virus (PPRV), and NiV polymerases. ERDRP-0519 forms more extensive interactions with Morbillivirus polymerases, whereas binding to NiV polymerase requires substantial RdRp motif rearrangements, likely incurring an energetic cost and resulting in reduced affinity. ERDRP-0519 binding impedes RNA synthesis by sterically blocking RNA and nucleotide binding. Guided by these insights, we designed GL22 and G671, ERDRP-0519 derivatives with extended moieties that engage additional cross-domain RdRp contacts in the NiV polymerase. These derivatives exert more extensive steric hindrance to RNA and nucleotide binding, enhancing biochemical inhibition potency. These findings elucidate the molecular mechanism of ERDRP-0519 action and guide structure-based inhibitor design.
リンク	Cell / PubMed:42061399
手法	EM (単粒子)
解像度	2.4 - 2.92 Å
構造データ	65442 9vxv EMDB-65442, PDB-9vxv: Cryo-EM Structure of Nipah Virus Polymerase in complex with ERDRP-0519 手法: EM (単粒子) / 解像度: 2.66 Å 65444 9vxx EMDB-65444, PDB-9vxx: Cryo-EM Structure of Measles Virus Polymerase in complex with ERDRP-0519 手法: EM (単粒子) / 解像度: 2.73 Å 65445 9vxy EMDB-65445, PDB-9vxy: Cryo-EM Structure of Nipah Virus Polymerase in complex with GL22 手法: EM (単粒子) / 解像度: 2.87 Å 65446 9vxz EMDB-65446, PDB-9vxz: Cryo-EM structure of Measles Virus L Protein bound by Phosphoprotein Tetramer 手法: EM (単粒子) / 解像度: 2.68 Å 65447 9vy0 EMDB-65447, PDB-9vy0: Cryo-EM Structure of Peste Des Petits Ruminants Virus Polymerase in complex with ERDRP-0519 手法: EM (単粒子) / 解像度: 2.71 Å 65448 9vy1 EMDB-65448, PDB-9vy1: Cryo-EM structure of Peste Des Petits Ruminants Virus L Protein bound by Phosphoprotein Tetramer 手法: EM (単粒子) / 解像度: 2.4 Å 68072 21xo EMDB-68072, PDB-21xo: Cryo-EM Structure of Nipah Virus Polymerase in complex with G671 手法: EM (単粒子) / 解像度: 2.92 Å
化合物	PDB-1e3h: SeMet derivative of Streptomyces antibioticus PNPase/GPSI enzyme ChemComp-ZN: Unknown entry PDB-1ef9: THE CRYSTAL STRUCTURE OF METHYLMALONYL COA DECARBOXYLASE COMPLEXED WITH 2S-CARBOXYPROPYL COA PDB-1et4: CRYSTAL STRUCTURE OF A VITAMIN B12 BINDING RNA APTAMER WITH LIGAND AT 2.3 A
由来	henipavirus nipahense (ウイルス) measles morbillivirus (ウイルス) measles virus genotype b3 (ウイルス) peste-des-petits-ruminants virus (ウイルス)
キーワード	VIRAL PROTEIN / Polymerase / inhibitor / nipah virus / complex / REPLICATION / Measles virus / RNA / Peste Des Petits Ruminants Virus