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In SARS coronaviruses, the non-structural protein 16 (nsp16) methylates the 5\u2019-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\u2019-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\u2019-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.<\/jats:p>","DOI":"10.1101\/2020.04.26.061705","type":"posted-content","created":{"date-parts":[[2020,4,27]],"date-time":"2020-04-27T06:35:11Z","timestamp":1587969311000},"source":"Crossref","is-referenced-by-count":9,"title":["Structural Basis of RNA Cap Modification by SARS-CoV-2 Coronavirus"],"prefix":"10.64898","author":[{"given":"Thiruselvam","family":"Viswanathan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shailee","family":"Arya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siu-Hong","family":"Chan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shan","family":"Qi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nan","family":"Dai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert A.","family":"Hromas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun-Gyu","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fatai","family":"Oladunni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis","family":"Martinez-Sobrido","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6372-5007","authenticated-orcid":false,"given":"Yogesh K.","family":"Gupta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024080405181761000_2020.04.26.061705v1.1","unstructured":"(2020) COVID-19 Coronavirus Pandemic, In https:\/\/www.worldometers.info\/coronavirus\/."},{"key":"2024080405181761000_2020.04.26.061705v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2012-7"},{"key":"2024080405181761000_2020.04.26.061705v1.3","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00078-11"},{"key":"2024080405181761000_2020.04.26.061705v1.4","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000863"},{"key":"2024080405181761000_2020.04.26.061705v1.5","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1201130109"},{"key":"2024080405181761000_2020.04.26.061705v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2675"},{"key":"2024080405181761000_2020.04.26.061705v1.7","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.14.7833-7838.2004"},{"key":"2024080405181761000_2020.04.26.061705v1.8","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002294"},{"key":"2024080405181761000_2020.04.26.061705v1.9","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1979"},{"key":"2024080405181761000_2020.04.26.061705v1.10","doi-asserted-by":"publisher","DOI":"10.1038\/nature09489"},{"key":"2024080405181761000_2020.04.26.061705v1.11","doi-asserted-by":"crossref","unstructured":"Hyde, J. 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