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Global efforts in drug and vaccine development to fight the disease have yielded vaccines and drug candidates to cure COVID-19. However, the spread of SARS-CoV-2 variants threatens the continued efficacy of these treatments. In order to address this, we interrogate the evolutionary history of the entire SARS-CoV-2 proteome to identify evolutionarily conserved functional sites that can inform the search for treatments with broader coverage across the coronavirus family.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Combining coronavirus family sequence information with the mutations observed in the current COVID-19 outbreak, we systematically and comprehensively define evolutionarily stable sites that may provide useful drug and vaccine targets and which are less likely to be compromised by the emergence of new virus strains. Several experimentally validated effective drugs interact with these proposed target sites. In addition, the same evolutionary information can prioritize cross reactive antigens that are useful in directing multi-epitope vaccine strategies to illicit broadly neutralizing immune responses to the betacoronavirus family. Although the results are focused on SARS-CoV-2, these approaches stem from evolutionary principles that are agnostic to the organism or infective agent.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>The results of this work are made interactively available at http:\/\/cov.lichtargelab.org.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Supplementary information<\/jats:title>\n                    <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btab406","type":"journal-article","created":{"date-parts":[[2021,5,26]],"date-time":"2021-05-26T15:22:39Z","timestamp":1622042559000},"page":"4033-4040","source":"Crossref","is-referenced-by-count":6,"title":["Identification of evolutionarily stable functional and immunogenic sites across the SARS-CoV-2 proteome and greater coronavirus family"],"prefix":"10.1093","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5769-2077","authenticated-orcid":false,"given":"Chen","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine , Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel M","family":"Konecki","sequence":"additional","affiliation":[{"name":"Quantitative and Computational Biosciences Graduate Program, Baylor College of Medicine , Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David C","family":"Marciano","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine , Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harikumar","family":"Govindarajan","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine , Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda M","family":"Williams","sequence":"additional","affiliation":[{"name":"Cancer and Cell Biology Graduate Program, Baylor College of Medicine , Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brigitta","family":"Wastuwidyaningtyas","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine , Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Bourquard","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine , Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Panagiotis","family":"Katsonis","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine , Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olivier","family":"Lichtarge","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine , Houston, TX 77030, USA"},{"name":"Quantitative and Computational Biosciences Graduate Program, Baylor College of Medicine , Houston, TX 77030, USA"},{"name":"Cancer and Cell Biology Graduate Program, Baylor College of Medicine , Houston, TX 77030, USA"},{"name":"Computational and Integrative Biomedical Research Center, Baylor College of Medicine , Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,5,27]]},"reference":[{"key":"2023051607095252500_btab406-B1","doi-asserted-by":"crossref","first-page":"254","DOI":"10.3390\/v12030254","article-title":"Preliminary identification of potential vaccine targets for the COVID-19 coronavirus (SARS-CoV-2) based on SARS-CoV immunological studies","volume":"12","author":"Ahmed","year":"2020","journal-title":"Viruses"},{"key":"2023051607095252500_btab406-B2","doi-asserted-by":"crossref","first-page":"E4195","DOI":"10.1073\/pnas.1305162110","article-title":"Prediction and experimental validation of enzyme substrate specificity in protein structures","volume":"110","author":"Amin","year":"2013","journal-title":"Proc. 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