{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T21:14:00Z","timestamp":1780521240247,"version":"3.54.1"},"reference-count":60,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,5,19]],"date-time":"2022-05-19T00:00:00Z","timestamp":1652918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health","award":["2020-1353"],"award-info":[{"award-number":["2020-1353"]}]},{"name":"Italian Ministry of Health","award":["H44I20000470002"],"award-info":[{"award-number":["H44I20000470002"]}]},{"name":"Fondazione Cariplo","award":["2020-1353"],"award-info":[{"award-number":["2020-1353"]}]},{"name":"Fondazione Cariplo","award":["H44I20000470002"],"award-info":[{"award-number":["H44I20000470002"]}]},{"name":"Regione Lombardia","award":["2020-1353"],"award-info":[{"award-number":["2020-1353"]}]},{"name":"Regione Lombardia","award":["H44I20000470002"],"award-info":[{"award-number":["H44I20000470002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Four endemic coronaviruses infect humans and cause mild symptoms. Because previous analyses were based on a limited number of sequences and did not control for effects that affect molecular dating, we re-assessed the timing of endemic coronavirus emergence. After controlling for recombination, selective pressure, and molecular clock model, we obtained similar tMRCA (time to the most recent common ancestor) estimates for the four coronaviruses, ranging from 72 (HCoV-229E) to 54 (HCoV-NL63) years ago. The split times of HCoV-229E and HCoV-OC43 from camel alphacoronavirus and bovine coronavirus were dated ~268 and ~99 years ago. The split times of HCoV-HKU1 and HCoV-NL63 could not be calculated, as their zoonoticic sources are unknown. To compare the timing of coronavirus emergence to that of another respiratory virus, we recorded the occurrence of influenza pandemics since 1500. Although there is no clear relationship between pandemic occurrence and human population size, the frequency of influenza pandemics seems to intensify starting around 1700, which corresponds with the initial phase of exponential increase of human population and to the emergence of HCoV-229E. The frequency of flu pandemics in the 19th century also suggests that the concurrence of HCoV-OC43 emergence and the Russian flu pandemic may be due to chance.<\/jats:p>","DOI":"10.3390\/v14051095","type":"journal-article","created":{"date-parts":[[2022,5,20]],"date-time":"2022-05-20T00:18:11Z","timestamp":1653005891000},"page":"1095","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Dating the Emergence of Human Endemic Coronaviruses"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9291-5352","authenticated-orcid":false,"given":"Diego","family":"Forni","sequence":"first","affiliation":[{"name":"Bioinformatics, Scientific Institute IRCCS E. MEDEA, 23842 Bosisio Parini, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2670-3532","authenticated-orcid":false,"given":"Rachele","family":"Cagliani","sequence":"additional","affiliation":[{"name":"Bioinformatics, Scientific Institute IRCCS E. MEDEA, 23842 Bosisio Parini, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uberto","family":"Pozzoli","sequence":"additional","affiliation":[{"name":"Bioinformatics, Scientific Institute IRCCS E. MEDEA, 23842 Bosisio Parini, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3911-1042","authenticated-orcid":false,"given":"Alessandra","family":"Mozzi","sequence":"additional","affiliation":[{"name":"Bioinformatics, Scientific Institute IRCCS E. MEDEA, 23842 Bosisio Parini, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Arrigoni","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Biosciences, University of Milan-Bicocca, 20126 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"De Gioia","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Biosciences, University of Milan-Bicocca, 20126 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5920-6191","authenticated-orcid":false,"given":"Mario","family":"Clerici","sequence":"additional","affiliation":[{"name":"Department of Physiopathology and Transplantation, University of Milan, 20122 Milan, Italy"},{"name":"Don Carlo Gnocchi Foundation ONLUS, IRCCS, 20148 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2267-5266","authenticated-orcid":false,"given":"Manuela","family":"Sironi","sequence":"additional","affiliation":[{"name":"Bioinformatics, Scientific Institute IRCCS E. MEDEA, 23842 Bosisio Parini, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.7150\/ijbs.45472","article-title":"Zoonotic Origins of Human Coronaviruses","volume":"16","author":"Ye","year":"2020","journal-title":"Int. J. Biol. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.tim.2016.09.001","article-title":"Molecular Evolution of Human Coronavirus Genomes","volume":"25","author":"Forni","year":"2017","journal-title":"Trends Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1038\/s41579-018-0118-9","article-title":"Origin and Evolution of Pathogenic Coronaviruses","volume":"17","author":"Cui","year":"2019","journal-title":"Nat. Rev. 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