{"doi":"10.1101/2020.04.26.061705","title":"Structural Basis of RNA Cap Modification by SARS-CoV-2 Coronavirus","abstract":"The novel severe acute respiratory syndrome coronoavirus-2 (SARS-CoV-2), the causative agent of COVID-19 illness, has caused over 2 million infections worldwide in four months. In SARS coronaviruses, the non-structural protein 16 (nsp16) methylates the 5'-end of virally encoded mRNAs to mimic cellular mRNAs, thus protecting the virus from host innate immune restriction. We report here the high-resolution structure of a ternary complex of full-length nsp16 and nsp10 of SARS-CoV-2 in the presence of cognate RNA substrate and a methyl donor, S-adenosyl methionine. The nsp16/nsp10 heterodimer was captured in the act of 2'-O methylation of the ribose sugar of the first nucleotide of SARS-CoV-2 mRNA. We reveal large conformational changes associated with substrate binding as the enzyme transitions from a binary to a ternary state. This structure provides new mechanistic insights into the 2'-O methylation of the viral mRNA cap. We also discovered a distantly located ligand-binding site unique to SARS-CoV-2 that may serve as an alternative target site for antiviral development.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":119459,"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":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9601,"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":240052,"name":"Shailee Arya","orcid":"0000-0002-7689-7411","position":1,"is_corresponding":false},{"id":240053,"name":"Siu‐Hong Chan","orcid":"0000-0002-9554-7273","position":2,"is_corresponding":false},{"id":240054,"name":"Shan Qi","orcid":"0000-0003-0175-6267","position":3,"is_corresponding":false},{"id":240055,"name":"Nan Dai","orcid":"0000-0003-3268-1835","position":4,"is_corresponding":false},{"id":240060,"name":"Robert Hromas","orcid":"0000-0002-1916-6276","position":5,"is_corresponding":false},{"id":555172,"name":"Jun-Gyu Park","orcid":null,"position":6,"is_corresponding":false},{"id":240058,"name":"Fatai S. Oladunni","orcid":"0000-0001-5050-0183","position":7,"is_corresponding":false},{"id":2423,"name":"Luis Martínez‐Sobrido","orcid":"0000-0001-7084-0804","position":8,"is_corresponding":false},{"id":240061,"name":"Yogesh K. Gupta","orcid":"0000-0001-6372-5007","position":9,"is_corresponding":false},{"id":240051,"name":"Thiruselvam Viswanathan","orcid":"0000-0001-9817-6730","position":0,"is_corresponding":true}],"reference_count":27,"raw_metadata":null,"created_at":"2026-07-18T23:14:08.313144Z","pmid":"32511383","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":[]}