{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T10:55:16Z","timestamp":1767178516769,"version":"build-2238731810"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1012812","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T00:00:00Z","timestamp":1739145600000}}],"reference-count":67,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T00:00:00Z","timestamp":1738713600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01GM138444"],"award-info":[{"award-number":["R01GM138444"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001062","name":"Wallace H. Coulter Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004063","name":"Knut och Alice Wallenbergs Stiftelse","doi-asserted-by":"publisher","award":["2020.209"],"award-info":[{"award-number":["2020.209"]}],"id":[{"id":"10.13039\/501100004063","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["1810762"],"award-info":[{"award-number":["1810762"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>Betacoronaviruses pose an ongoing pandemic threat. Antigenic evolution of the SARS-CoV-2 virus has shown that much of the spontaneous antibody response is narrowly focused rather than broadly neutralizing against even SARS-CoV-2 variants, let alone future threats. One way to overcome this is by focusing the antibody response against better-conserved regions of the viral spike protein. This has been demonstrated empirically in prior work, but we posit that systematic design tools will further potentiate antigenic focusing approaches. Here, we present a design approach to predict stable chimeras between SARS-CoV-2 and other coronaviruses, creating synthetic spike proteins that display a desired conserved region, in this case S2, and vary other regions. We leverage AlphaFold to predict chimeric structures and create a new metric for scoring chimera stability based on AlphaFold outputs. We evaluated 114 candidate spike chimeras using this approach. Top chimeras were further evaluated using molecular dynamics simulation as an intermediate validation technique, showing good stability compared to low-scoring controls. Experimental testing of five predicted-stable and two predicted-unstable chimeras confirmed 5\/7 predictions, with one intermediate result. This demonstrates the feasibility of the underlying approach, which can be used to design custom immunogens to focus the immune response against a desired viral glycoprotein epitope.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1012812","type":"journal-article","created":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T13:43:34Z","timestamp":1738763014000},"page":"e1012812","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Structural prediction of chimeric immunogen candidates to elicit targeted antibodies against betacoronaviruses"],"prefix":"10.1371","volume":"21","author":[{"given":"Jamel","family":"Simpson","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3111-8103","authenticated-orcid":true,"given":"Peter 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Cai","year":"2020","journal-title":"Science"},{"issue":"6501","key":"pcbi.1012812.ref052","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1126\/science.abb9983","article-title":"Site-specific glycan analysis of the SARS-CoV-2 spike","volume":"369","author":"Y Watanabe","year":"2020","journal-title":"Science"},{"issue":"10","key":"pcbi.1012812.ref053","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1038\/s41557-021-00758-3","article-title":"A glycan gate controls opening of the SARS-CoV-2 spike protein","volume":"13","author":"T Sztain","year":"2021","journal-title":"Nat Chem"},{"issue":"6483","key":"pcbi.1012812.ref054","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1126\/science.abb2507","article-title":"Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation","volume":"367","author":"D 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Evans","year":"2004","journal-title":"bioRxiv"},{"issue":"1","key":"pcbi.1012812.ref058","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1186\/s12859-019-3019-7","article-title":"HH-suite3 for fast remote homology detection and deep protein annotation","volume":"20","author":"M Steinegger","year":"2019","journal-title":"BMC Bioinformatics"},{"issue":"1","key":"pcbi.1012812.ref059","doi-asserted-by":"crossref","first-page":"2542","DOI":"10.1038\/s41467-018-04964-5","article-title":"Clustering huge protein sequence sets in linear time","volume":"9","author":"M Steinegger","year":"2018","journal-title":"Nat Commun"},{"issue":"W1","key":"pcbi.1012812.ref060","doi-asserted-by":"crossref","first-page":"W200","DOI":"10.1093\/nar\/gky448","article-title":"HMMER web server: 2018 update","volume":"46","author":"SC Potter","year":"2018","journal-title":"Nucleic Acids 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