9MZH

Cryo-EM structure of the Nipah virus polymerase containing the connecting domain

Summary for 9MZH

• Entry DOI: 10.2210/pdb9mzh/pdb
• Related: 9COK 9MUW
• EMDB information: 45896
• Descriptor: Phosphoprotein, RNA-directed RNA polymerase L (2 entities in total)
• Functional Keywords: nipah virus, polymerase, connecting domain, viral protein, transferase
• Biological source: Henipavirus nipahense; More
• Total number of polymer chains: 7
• Total formula weight: 941409.33

Authors

Chen, Z.H.,Liang, B. (deposition date: 2025-01-23, release date: 2025-07-30, Last modification date: 2025-11-05)

Primary citation

Chen, Z.,Quirit Dudley, J.,Deniston, C.,Buffalo, C.Z.,Patra, D.,Cao, D.,Hunt, J.,Rohaim, A.,Sengupta, D.,Wen, L.,Tsang, T.,Xie, L.,DiDonato, M.,Spraggon, G.,Clifton, M.C.,Jarrousse, N.,Straimer, J.,Liang, B.
Cryo-EM structures of Nipah virus polymerases and high-throughput RdRp assay development enable anti-NiV drug discovery.
Nat Commun, 16:6655-6655, 2025

PubMed Abstract: Transcription and replication of the Nipah virus (NiV) are driven by the large protein (L) together with its essential co-factor phosphoprotein (P). L encodes all the viral enzymatic functions, including RNA-dependent RNA polymerase (RdRp) activity, while the tetrameric P is multi-modular. Here, we investigate the molecular mechanism of the NiV polymerase and build tools for anti-NiV drug discovery. We analyze and compare multiple cryo-EM structures of both full-length and truncated NiV polymerases from the Malaysia and Bangladesh strains. We identify two conserved loops in the polyribonucleotidyltransferase (PRNTase) domain of L and the binding between RdRp-PRNTase and CD domains. To further assess the mechanism of NiV polymerase activity, we establish a highly sensitive radioactive-labeled RNA synthesis assay and identify a back-priming activity in the NiV polymerase as well as a fluorescence and luminescent-based non-radioactive polymerase assay to enable high-throughput screening for L protein inhibitors. The combination of structural analysis and the development of both high-sensitive and high-throughput biochemical assays will enable the identification of new direct-acting antiviral candidates for treating highly pathogenic henipaviruses.

PubMed: 40683863
DOI: 10.1038/s41467-025-61764-4

Experimental method

ELECTRON MICROSCOPY (2.99 Å)