ジャーナル: Cell / 年: 2025 タイトル: Structures of the measles virus polymerase complex with non-nucleoside inhibitors and mechanism of inhibition. 著者: Yiru Wang / Lixia Zhao / Yi Zhang / Xiuxia Gao / Yannan Wang / Wenping Shi / Roger D Kornberg / Heqiao Zhang / 要旨: The measles virus (MeV), a highly contagious non-segmented negative-sense RNA virus in the Paramyxoviridae family, causes millions of infections annually, with no approved antivirals available. The ...The measles virus (MeV), a highly contagious non-segmented negative-sense RNA virus in the Paramyxoviridae family, causes millions of infections annually, with no approved antivirals available. The viral polymerase complex, comprising the large (L) protein and the tetrameric phosphoprotein (P), is a key antiviral target. We determined the cryo-electron microscopy structures of the MeV polymerase complex alone and bound to two non-nucleoside inhibitors, ERDRP-0519 and AS-136A. Inhibitor binding induces a conformational change in the catalytic loop, allosterically locking the polymerase in an inactive "GDN-out" state. These findings led to the proposal that ERDRP-0519 would also be effective against Nipah virus (NiV), a highly pathogenic virus with no available antivirals. This proposal was confirmed by structure determination of the NiV polymerase complex and by inhibition of transcription.
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