{"doi":"10.1101/2020.07.08.194084","title":"Structural basis for helicase-polymerase coupling in the SARS-CoV-2 replication-transcription complex","abstract":"SARS-CoV-2 is the causative agent of the 2019-2020 pandemic. The SARS-CoV-2 genome is replicated-transcribed by the RNA-dependent RNA polymerase holoenzyme (subunits nsp7/nsp82/nsp12) along with a cast of accessory factors. One of these factors is the nsp13 helicase. Both the holo-RdRp and nsp13 are essential for viral replication and are targets for treating the disease COVID-19. Here we present cryo-electron microscopic structures of the SARS-CoV-2 holo-RdRp with an RNA template-product in complex with two molecules of the nsp13 helicase. The Nidovirus-order-specific N-terminal domains of each nsp13 interact with the N-terminal extension of each copy of nsp8. One nsp13 also contacts the nsp12-thumb. The structure places the nucleic acid-binding ATPase domains of the helicase directly in front of the replicating-transcribing holo-RdRp, constraining models for nsp13 function. We also observe ADP-Mg2+ bound in the nsp12 N-terminal nidovirus RdRp-associated nucleotidyltransferase domain, detailing a new pocket for anti-viral therapeutic development.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":118696,"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":47,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9544,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":258068,"name":"Brandon Malone","orcid":"0000-0001-7752-9824","position":1,"is_corresponding":false},{"id":481685,"name":"Eliza Llewellyn","orcid":"0000-0002-0346-0139","position":2,"is_corresponding":false},{"id":313625,"name":"Michael Grasso","orcid":"0000-0002-2076-867X","position":3,"is_corresponding":false},{"id":315770,"name":"Patrick M. M. Shelton","orcid":null,"position":4,"is_corresponding":false},{"id":471220,"name":"Paul Dominic B. Olinares","orcid":"0000-0002-3429-6618","position":5,"is_corresponding":false},{"id":258059,"name":"Kashyap Maruthi","orcid":"0000-0001-5290-4413","position":6,"is_corresponding":false},{"id":253671,"name":"Edward T. Eng","orcid":"0000-0002-8014-7269","position":7,"is_corresponding":false},{"id":551817,"name":"Hasan Vatandaslar","orcid":"0000-0002-8405-9055","position":8,"is_corresponding":false},{"id":51698,"name":"Brian T. Chait","orcid":"0000-0003-3524-557X","position":9,"is_corresponding":false},{"id":313628,"name":"Tarun M. Kapoor","orcid":"0000-0003-0628-211X","position":10,"is_corresponding":false},{"id":258065,"name":"Seth A. Darst","orcid":"0000-0002-8241-3153","position":11,"is_corresponding":false},{"id":461537,"name":"Elizabeth A. Campbell","orcid":"0000-0002-1332-128X","position":12,"is_corresponding":false},{"id":258067,"name":"James Chen","orcid":"0000-0002-2311-003X","position":0,"is_corresponding":true}],"reference_count":94,"raw_metadata":null,"created_at":"2026-07-18T23:14:03.409507Z","pmid":"32676607","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":[]}