{"doi":"10.1016/j.cell.2024.12.021","title":"Structural and functional analysis of the Nipah virus polymerase complex","abstract":"Nipah virus (NiV) is a bat-borne, zoonotic RNA virus that is highly pathogenic in humans. The NiV polymerase, which mediates viral genome replication and mRNA transcription, is a promising drug target. We determined the cryoelectron microscopy (cryo-EM) structure of the NiV polymerase complex, comprising the large protein (L) and phosphoprotein (P), and performed structural, biophysical, and in-depth functional analyses of the NiV polymerase. The L protein assembles with a long P tetrameric coiled-coil that is capped by a bundle of ⍺-helices that we show are likely dynamic in solution. Docking studies with a known L inhibitor clarify mechanisms of antiviral drug resistance. In addition, we identified L protein features that are required for both transcription and RNA replication and mutations that have a greater impact on RNA replication than on transcription. Our findings have the potential to aid in the rational development of drugs to combat NiV infection.","journal":"Cell","year":2025,"id":509443,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":33,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9477,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1363509,"name":"Heesu Kim","orcid":"0000-0001-7769-2699","position":1,"is_corresponding":false},{"id":630376,"name":"Pan Yang","orcid":"0000-0002-2431-0252","position":2,"is_corresponding":false},{"id":1219683,"name":"Zishuo Yu","orcid":"0000-0001-6713-3113","position":3,"is_corresponding":false},{"id":479186,"name":"Barbara Ludeke","orcid":"0000-0002-6616-5866","position":4,"is_corresponding":false},{"id":1364340,"name":"Shawna Mobilia","orcid":null,"position":5,"is_corresponding":false},{"id":553552,"name":"Junhua Pan","orcid":"0000-0002-0070-955X","position":6,"is_corresponding":false},{"id":324095,"name":"Margaret M. Stratton","orcid":"0000-0003-2686-9022","position":7,"is_corresponding":false},{"id":696373,"name":"Yuemin Bian","orcid":"0000-0002-5845-772X","position":8,"is_corresponding":false},{"id":479188,"name":"Rachel Fearns","orcid":"0000-0003-0783-7498","position":9,"is_corresponding":false},{"id":553557,"name":"Jonathan Abraham","orcid":"0000-0002-7937-3920","position":10,"is_corresponding":false},{"id":1363508,"name":"Side Hu","orcid":"0000-0001-9320-5360","position":0,"is_corresponding":true}],"reference_count":74,"raw_metadata":null,"created_at":"2026-07-19T02:47:24.513904Z","pmid":"39837328","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}