{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T12:41:18Z","timestamp":1769517678586,"version":"3.49.0"},"reference-count":42,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T00:00:00Z","timestamp":1693526400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FONDAZIONE DI SARDEGNA bando 2022\u20132023 for the Dipartimento di Scienze Biomediche\u2014UNISS","award":["CRP\/BRA20-03"],"award-info":[{"award-number":["CRP\/BRA20-03"]}]},{"name":"FONDAZIONE DI SARDEGNA bando 2022\u20132023 for the Dipartimento di Scienze Biomediche\u2014UNISS","award":["RP12117A7670A1E8"],"award-info":[{"award-number":["RP12117A7670A1E8"]}]},{"name":"Ricerca e Innovazione","award":["CRP\/BRA20-03"],"award-info":[{"award-number":["CRP\/BRA20-03"]}]},{"name":"Ricerca e Innovazione","award":["RP12117A7670A1E8"],"award-info":[{"award-number":["RP12117A7670A1E8"]}]},{"name":"CRP-ICGEB RESEARCH GRANT 2020 Project","award":["CRP\/BRA20-03"],"award-info":[{"award-number":["CRP\/BRA20-03"]}]},{"name":"CRP-ICGEB RESEARCH GRANT 2020 Project","award":["RP12117A7670A1E8"],"award-info":[{"award-number":["RP12117A7670A1E8"]}]},{"name":"Sapienza","award":["CRP\/BRA20-03"],"award-info":[{"award-number":["CRP\/BRA20-03"]}]},{"name":"Sapienza","award":["RP12117A7670A1E8"],"award-info":[{"award-number":["RP12117A7670A1E8"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The XBB.1.16 SARS-CoV-2 variant, also known as Arcturus, is a recent descendant lineage of the recombinant XBB (nicknamed Gryphon). Compared to its direct progenitor, XBB.1, XBB.1.16 carries additional spike mutations in key antigenic sites, potentially conferring an ability to evade the immune response compared to other circulating lineages. In this context, we conducted a comprehensive genome-based survey to gain a detailed understanding of the evolution and potential dangers of the XBB.1.16 variant, which became dominant in late June. Genetic data indicates that the XBB.1.16 variant exhibits an evolutionary background with limited diversification, unlike dangerous lineages known for rapid changes. The evolutionary rate of XBB.1.16, which amounts to 3.95 \u00d7 10\u22124 subs\/site\/year, is slightly slower than that of its direct progenitors, XBB and XBB.1.5, which have been circulating for several months. A Bayesian Skyline Plot reconstruction suggests that the peak of genetic variability was reached in early May 2023, and currently, it is in a plateau phase with a viral population size similar to the levels observed in early March. Structural analyses indicate that, overall, the XBB.1.16 variant does not possess structural characteristics markedly different from those of the parent lineages, and the theoretical affinity for ACE2 does not seem to change among the compared variants. In conclusion, the genetic and structural analyses of SARS-CoV-2 XBB.1.16 do not provide evidence of its exceptional danger or high expansion capability. Detected differences with previous lineages are probably due to genetic drift, which allows the virus constant adaptability to the host, but they are not necessarily connected to a greater danger. Nevertheless, continuous genome-based monitoring is essential for a better understanding of its descendants and other lineages.<\/jats:p>","DOI":"10.3390\/ijms241713573","type":"journal-article","created":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T08:19:39Z","timestamp":1693556379000},"page":"13573","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Integrative Genome-Based Survey of the SARS-CoV-2 Omicron XBB.1.16 Variant"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3501-714X","authenticated-orcid":false,"given":"Fabio","family":"Scarpa","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilenia","family":"Azzena","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy"},{"name":"Department of Veterinary Medicine, University of Sassari, 07100 Sassari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Ciccozzi","sequence":"additional","affiliation":[{"name":"Unit of Medical Statistics and Molecular Epidemiology, Universit\u00e0 Campus Bio-Medico di Roma, 00128 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5849-7326","authenticated-orcid":false,"given":"Marta","family":"Giovanetti","sequence":"additional","affiliation":[{"name":"Instituto Rene Rachou Funda\u00e7\u00e3o Oswaldo Cruz, Belo Horizonte 30190-009, MG, Brazil"},{"name":"Sciences and Technologies for Sustainable Development and One Health, Universit\u00e0 Campus Bio-Medico di Roma, 00128 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Locci","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy"},{"name":"Department of Veterinary Medicine, University of Sassari, 07100 Sassari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5042-4851","authenticated-orcid":false,"given":"Marco","family":"Casu","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Sassari, 07100 Sassari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6190-612X","authenticated-orcid":false,"given":"Pier Luigi","family":"Fiori","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy"},{"name":"Azienza Ospedaliera Universitaria (AOU) Sassari, 07100 Sassari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5401-135X","authenticated-orcid":false,"given":"Alessandra","family":"Borsetti","sequence":"additional","affiliation":[{"name":"National HIV\/AIDS Research Center (CNAIDS), National Institute of Health, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7870-9744","authenticated-orcid":false,"given":"Eleonora","family":"Cella","sequence":"additional","affiliation":[{"name":"Burnett School of Biomedical Sciences, University of Central Florida, Orlando, FL 32816, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miriana","family":"Quaranta","sequence":"additional","affiliation":[{"name":"Department of Biochemical Sciences \u201cA. Rossi Fanelli\u201d, Sapienza Universit\u00e0 di Roma, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6822-4022","authenticated-orcid":false,"given":"Stefano","family":"Pascarella","sequence":"additional","affiliation":[{"name":"Department of Biochemical Sciences \u201cA. 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J. Infect. Dis."},{"key":"ref_3","unstructured":"World Health Organization (2023, July 24). WHO Director-General\u2019s Opening Remarks at the Media Briefing on COVID-19\u201411 March 2020. Available online: https:\/\/www.who.int\/director-general\/speeches\/detail\/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---11-march-2020."},{"key":"ref_4","unstructured":"World Health Organization (2023, July 24). Weekly Epidemiological Update on COVID-19\u201427 July 2023. Available online: https:\/\/www.who.int\/publications\/m\/item\/weekly-epidemiological-update-on-covid-19---27-july-2023."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1002\/jmv.27519","article-title":"The unresolved question on COVID-19 virus origin: The three cards game?","volume":"94","author":"Borsetti","year":"2022","journal-title":"J. Med. Virol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1038\/s41586-020-2368-8","article-title":"Structure of replicating SARS-CoV-2 polymerase","volume":"584","author":"Hillen","year":"2020","journal-title":"Nature"},{"key":"ref_7","unstructured":"World Health Organization (2023, July 24). XBB.1.16 Initial Risk Assessment, 17 April 2023. Available online: https:\/\/www.who.int\/docs\/default-source\/coronaviruse\/21042023xbb.1.16ra-v2.pdf?sfvrsn=84577350_1."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"World Health Organization (2023, July 20). WHO Tracking SARS-CoV-2 Variants. Available online: https:\/\/www.who.int\/activities\/tracking-SARS-CoV-2-variants.","DOI":"10.1038\/s41592-023-01833-y"},{"key":"ref_9","unstructured":"GISAID (2023, July 20). Genomic Epidemiology of SARS-CoV-2 with Subsampling Focused Globally over the Past 6 Months. Available online: https:\/\/gisaid.org\/phylodynamics\/global\/nextstrain\/."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e28625","DOI":"10.1002\/jmv.28625","article-title":"Genome-based comparison between the recombinant SARS-CoV-2 XBB and its parental lineages","volume":"95","author":"Scarpa","year":"2023","journal-title":"J. Med. Virol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Scarpa, F., Azzena, I., Locci, C., Casu, M., Fiori, P.L., Ciccozzi, A., Angeletti, S., Imperia, E., Giovanetti, M., and Maruotti, A. (2023). Molecular In-Depth on the Epidemiological Expansion of SARS-CoV-2 XBB.1.5. Microorganisms, 11.","DOI":"10.3390\/microorganisms11040912"},{"key":"ref_12","unstructured":"World Health Organization (2023, July 24). XBB.1.16 Updated Risk Assessment, 5 June 2023. Available online: https:\/\/www.who.int\/docs\/default-source\/coronaviruse\/05062023xbb.1.16.pdf?sfvrsn=f1845468_3."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.cell.2022.12.018","article-title":"Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants","volume":"186","author":"Wang","year":"2023","journal-title":"Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1056\/NEJMc2214302","article-title":"Efficacy of Antiviral Agents against Omicron Subvariants BQ.1.1 and XBB","volume":"388","author":"Imai","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_15","unstructured":"(2023, July 20). GISAID Lineage Comparison. Available online: https:\/\/gisaid.org\/lineage-comparison\/."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Magazine, N., Zhang, T., Wu, Y., McGee, M.C., Veggiani, G., and Huang, W. (2022). Mutations and Evolution of the SARS-CoV-2 Spike Protein. Viruses, 14.","DOI":"10.3390\/v14030640"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Scarpa, F., Locci, C., Azzena, I., Casu, M., Fiori, P.L., Ciccozzi, A., Giovanetti, M., Quaranta, M., Ceccarelli, G., and Pascarella, S. (2023). SARS-CoV-2 Recombinants: Genomic Comparison between XBF and Its Parental Lineages. Microorganisms, 11.","DOI":"10.3390\/microorganisms11071824"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e28119","DOI":"10.1002\/jmv.28119","article-title":"On the SARS-CoV-2 BA.2.75 variant: A genetic and structural point of view","volume":"95","author":"Scarpa","year":"2023","journal-title":"J. Med. Virol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Scarpa, F., Sanna, D., Benvenuto, D., Borsetti, A., Azzena, I., Casu, M., Fiori, P.L., Giovanetti, M., Maruotti, A., and Ceccarelli, G. (2022). Genetic and Structural Data on the SARS-CoV-2 Omicron BQ.1 Variant Reveal Its Low Potential for Epidemiological Expansion. Int. J. Mol. Sci., 23.","DOI":"10.1101\/2022.11.11.516052"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e28714","DOI":"10.1002\/jmv.28714","article-title":"Genome-based survey of the SARS-CoV-2 BF.7 variant from Asia","volume":"95","author":"Scarpa","year":"2023","journal-title":"J. Med. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"292","DOI":"10.3390\/idr15030029","article-title":"SARS-CoV CH.1.1 Variant: Genomic and Structural Insight","volume":"15","author":"Bazzani","year":"2023","journal-title":"Infect. Dis. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1080\/20477724.2020.1725339","article-title":"The global spread of 2019-nCoV: A molecular evolutionary analysis","volume":"114","author":"Benvenuto","year":"2020","journal-title":"Pathog. Glob. Health"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1169547","DOI":"10.3389\/fmicb.2023.1169547","article-title":"Respiratory viruses interacting with cells: The importance of electrostatics","volume":"14","author":"Lauster","year":"2023","journal-title":"Front. Microbiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1093\/molbev\/mst010","article-title":"MAFFT Multiple sequence alignment software version 7: Improvements in performance and usability","volume":"30","author":"Katoh","year":"2013","journal-title":"Mol. Biol. Evol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1093\/bioinformatics\/bts091","article-title":"UGENE Team. Unipro UGENE: A unified bioinformatics toolkit","volume":"28","author":"Okonechnikov","year":"2012","journal-title":"Bioinformatics"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1038\/nmeth.2109","article-title":"jModelTest 2: More models, new heuristics and parallel computing","volume":"9","author":"Darriba","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Drummond, A.J., and Rambaut, A. (2007). BEAST: Bayesian evolutionary analysis by sampling trees. BMC Evol. Biol., 7.","DOI":"10.1186\/1471-2148-7-214"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1080\/01621459.1995.10476572","article-title":"Bayes factors","volume":"90","author":"Kass","year":"1995","journal-title":"J. Am. Stat. Assoc."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1093\/sysbio\/syy032","article-title":"Posterior summarisation in Bayesian phylogenetics using Tracer 1.7","volume":"67","author":"Rambaut","year":"2018","journal-title":"Syst. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/978-1-4939-7231-9_4","article-title":"Protein structure modeling with MODELLER","volume":"1654","author":"Webb","year":"2017","journal-title":"Methods Mol. Biol."},{"key":"ref_31","unstructured":"Schrodinger, LLC (The PyMOL Molecular Graphics System, 2015). The PyMOL Molecular Graphics System, Version 1.8."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4168","DOI":"10.1093\/bioinformatics\/btz184","article-title":"FoldX 5.0: Working with RNA, small molecules and a new graphical interface","volume":"35","author":"Delgado","year":"2019","journal-title":"Bioinformatics"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1021\/ct100578z","article-title":"PROPKA3: Consistent treatment of internal and surface residues in empirical p K a predictions","volume":"7","author":"Olsson","year":"2011","journal-title":"J. Chem. Theory Comput."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1002\/pro.3280","article-title":"Improvements to the APBS biomolecular solvation software suite","volume":"27","author":"Jurrus","year":"2018","journal-title":"Protein Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1021\/acs.jcim.1c01269","article-title":"SURFMAP: A Software for Mapping in Two Dimensions Protein Surface Features","volume":"62","author":"Schweke","year":"2022","journal-title":"J. Chem. Inf. Model."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"W322","DOI":"10.1093\/nar\/gkz397","article-title":"HawkDock: A web server to predict and analyze the protein\u2013protein complex based on computational docking and MM\/GBSA","volume":"47","author":"Weng","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"btw514","DOI":"10.1093\/bioinformatics\/btw514","article-title":"PRODIGY: A web server for predicting the binding affinity of protein\u2013protein complexes","volume":"32","author":"Xue","year":"2016","journal-title":"Bioinformatics"},{"key":"ref_38","first-page":"134110","article-title":"Heterogeneous parallelization and acceleration of molecular dynamics simulations in GROMACS","volume":"153","author":"Zhmurov","year":"2020","journal-title":"Chem. Phys."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1950","DOI":"10.1002\/prot.22711","article-title":"Improved side-chain torsion potentials for the Amber ff99SB protein force field","volume":"78","author":"Piana","year":"2010","journal-title":"Proteins Struct. Funct. Genet."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Humphrey, W., Dalke, A., and Schulten, K. (1996). VMD: Visual molecular dynamics. J. Mol. Graph., 14.","DOI":"10.1016\/0263-7855(96)00018-5"},{"key":"ref_41","unstructured":"Turner, P. (XMGRACE, 2005). XMGRACE, Version 5.1.19."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"80","DOI":"10.2307\/3001968","article-title":"Individual Comparisons by Ranking Methods","volume":"1","author":"Wilcoxon","year":"1945","journal-title":"Biom. Bull."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/17\/13573\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:45:02Z","timestamp":1760129102000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/17\/13573"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,1]]},"references-count":42,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["ijms241713573"],"URL":"https:\/\/doi.org\/10.3390\/ijms241713573","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,1]]}}}