{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:42:26Z","timestamp":1790656946959,"version":"4.1.0"},"reference-count":67,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T00:00:00Z","timestamp":1761004800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>The continuous evolution of SARS-CoV-2 has led to the emergence of several variants representing significant challenges for public health. Many studies highlight the relevance of phylogenetic inference or mutational pattern analysis to understand the evolutionary relatedness of viral variants and to estimate the potential effect of new mutations on viral transmission, virulence and antigenicity. Here we describe an evolutionary investigation approach combined with mutational analyses of SARS-CoV-2 Spike gene to annotate and potentially track important amino acid site variation of specific functional domain relevant for viral survival. This approach was applied on XBB*, EG* and BA* and their sub-lineages (see materials and methods) available from GISAID. In addition, we considered the major variants of concern (Alpha, Delta, Omicron) and Wuhan-Hu-1 strain as references. Maximum likelihood phylogenetic tree was constructed from the complete dataset while selection pressure and mutational analyses were conducted on single variants separately. The obtained phylogenetic tree of Spike amino acid gene sequence showed a clear separation of viral variants as well as their expected appearance order. This result supported the significance of selection pressure analyses outcomes combined with amino acid mutational frequencies where in many cases they showed a linear and parallel trend. This allowed also to hypothesize the potential importance of low-frequency mutations in new potential virus variants. This study constitutes an asset of important insights to be considered in regular monitoring programs. In addition, the analysis framework described here introduces a starting point for further standardization, optimization and application on different data types and in large-scale studies.<\/jats:p>","DOI":"10.1371\/journal.pone.0333093","type":"journal-article","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T17:42:38Z","timestamp":1761068558000},"page":"e0333093","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Investigating the evolutionary dynamics and mutational pattern of SARS-CoV-2 spike gene on selected SARS-CoV-2 variants"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4419-0729","authenticated-orcid":true,"given":"Bachir","family":"Balech","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Lo Presti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Telegrafo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Maisto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela","family":"Giombini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Di Martino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigina","family":"Ambrosio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Apollonia","family":"Tullo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Stefanelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the Italian Genomic Laboratory Network","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,10,21]]},"reference":[{"key":"pone.0333093.ref001","unstructured":"European Centre for Disease Prevention and Control. SARS-CoV-2 variants of concern as of 27 September 2024. https:\/\/www.ecdc.europa.eu\/en\/covid-19\/variants-concern Accessed 2025 September 5."},{"key":"pone.0333093.ref002","unstructured":"Lineage List. https:\/\/cov-lineages.org\/lineage_list.html Accessed 2025 September 5."},{"key":"pone.0333093.ref003","unstructured":"World Health Organization. Tracking SARS-CoV-2 variants. https:\/\/www.who.int\/activities\/tracking-SARS-CoV-2-variants. Accessed 2025 September 5."},{"issue":"2","key":"pone.0333093.ref004","first-page":"90","article-title":"The Omicron XBB.1 Variant and Its Descendants: Genomic Mutations, Rapid Dissemination and Notable Characteristics","volume":"13","author":"R Giancotti","year":"2024","journal-title":"Biology (Basel)"},{"key":"pone.0333093.ref005","unstructured":"Istituto Superiore di Sanit\u00e0. Stima della prevalenza delle varianti di SARS-CoV-2 in Italia. https:\/\/www.epicentro.iss.it\/coronavirus\/pdf\/sars-cov-2-monitoraggio-varianti-indagini-rapide-4-aprile-2023.pdf"},{"key":"pone.0333093.ref006","unstructured":"Istituto Superiore di Sanit\u00e0. Stima della prevalenza delle principali varianti del virus SARS-CoV-2 circolanti in Italia. https:\/\/www.epicentro.iss.it\/coronavirus\/pdf\/sars-cov-2-monitoraggio-varianti-indagini-rapide-agosto-2023.pdf. Accessed 2023 August."},{"key":"pone.0333093.ref007","unstructured":"World Health Organization. Accessed September 05, 2025. Available from: https:\/\/www.who.int\/"},{"key":"pone.0333093.ref008","unstructured":"Istituto Superiore di Sanit\u00e0. Stima della prevalenza delle principali varianti del virus SARS-CoV-2 circolanti in Italia. https:\/\/www.epicentro.iss.it\/coronavirus\/pdf\/sars-cov-2-monitoraggio-varianti-indagini-rapide-settembre-2023.pdf. Accessed 2023 September."},{"issue":"11","key":"pone.0333093.ref009","doi-asserted-by":"crossref","DOI":"10.1016\/S1473-3099(23)00575-3","article-title":"Transmissibility, infectivity, and immune evasion of the SARS-CoV-2 BA.2.86 variant","volume":"23","author":"K Uriu","year":"2023","journal-title":"Lancet Infect Dis"},{"issue":"11","key":"pone.0333093.ref010","doi-asserted-by":"crossref","DOI":"10.1016\/S1473-3099(23)00588-1","article-title":"Sensitivity of the SARS-CoV-2 BA.2.86 variant to prevailing neutralising antibody responses","volume":"23","author":"DJ Sheward","year":"2023","journal-title":"Lancet Infect Dis"},{"issue":"11","key":"pone.0333093.ref011","doi-asserted-by":"crossref","DOI":"10.1016\/S1473-3099(23)00620-5","article-title":"Tracing the new SARS-CoV-2 variant BA.2.86 in the community through wastewater surveillance in Bangkok, Thailand","volume":"23","author":"DL Wannigama","year":"2023","journal-title":"Lancet Infect Dis"},{"issue":"11","key":"pone.0333093.ref012","doi-asserted-by":"crossref","DOI":"10.1016\/S1473-3099(23)00573-X","article-title":"Antigenicity and infectivity characterisation of SARS-CoV-2 BA.2.86","volume":"23","author":"S Yang","year":"2023","journal-title":"Lancet Infect Dis"},{"issue":"7992","key":"pone.0333093.ref013","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1038\/s41586-023-06750-w","article-title":"Antigenicity and receptor affinity of SARS-CoV-2 BA.2.86 spike","volume":"624","author":"Q Wang","year":"2023","journal-title":"Nature"},{"issue":"4","key":"pone.0333093.ref014","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1038\/s41592-023-01769-3","article-title":"Outbreak.info genomic reports: scalable and dynamic surveillance of SARS-CoV-2 variants and mutations","volume":"20","author":"K Gangavarapu","year":"2023","journal-title":"Nat Methods"},{"issue":"3","key":"pone.0333093.ref015","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1007\/s42770-022-00743-z","article-title":"Spike protein of SARS-CoV-2 variants: a brief review and practical implications","volume":"53","author":"KL Candido","year":"2022","journal-title":"Braz J Microbiol"},{"issue":"3","key":"pone.0333093.ref016","doi-asserted-by":"crossref","first-page":"640","DOI":"10.3390\/v14030640","article-title":"Mutations and Evolution of the SARS-CoV-2 Spike Protein","volume":"14","author":"N Magazine","year":"2022","journal-title":"Viruses"},{"issue":"9","key":"pone.0333093.ref017","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1038\/s41401-020-0485-4","article-title":"Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19","volume":"41","author":"Y Huang","year":"2020","journal-title":"Acta Pharmacol Sin"},{"key":"pone.0333093.ref018","doi-asserted-by":"crossref","first-page":"5556","DOI":"10.1016\/j.csbj.2021.10.004","article-title":"N-terminal domain mutations of the spike protein are structurally implicated in epitope recognition in emerging SARS-CoV-2 strains","volume":"19","author":"A Klinakis","year":"2021","journal-title":"Computational and Structural Biotechnology Journal"},{"issue":"1","key":"pone.0333093.ref019","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1080\/22221751.2020.1719902","article-title":"Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan","volume":"9","author":"JF-W Chan","year":"2020","journal-title":"Emerg Microbes Infect"},{"issue":"1","key":"pone.0333093.ref020","doi-asserted-by":"crossref","first-page":"109","DOI":"10.3390\/v13010109","article-title":"Domains and Functions of Spike Protein in Sars-Cov-2 in the Context of Vaccine Design","volume":"13","author":"X Xia","year":"2021","journal-title":"Viruses"},{"issue":"1","key":"pone.0333093.ref021","doi-asserted-by":"crossref","first-page":"5333","DOI":"10.1038\/s41467-021-25589-1","article-title":"Sequences in the cytoplasmic tail of SARS-CoV-2 Spike facilitate expression at the cell surface and syncytia formation","volume":"12","author":"J Cattin-Ortol\u00e1","year":"2021","journal-title":"Nat Commun"},{"issue":"8","key":"pone.0333093.ref022","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.3390\/pathogens12081047","article-title":"Timeline of SARS-CoV-2 Transmission in Sabah, Malaysia: Tracking the Molecular Evolution","volume":"12","author":"KN Balakrishnan","year":"2023","journal-title":"Pathogens"},{"issue":"4","key":"pone.0333093.ref023","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.01140-21","article-title":"Evolution, Mode of Transmission, and Mutational Landscape of Newly Emerging SARS-CoV-2 Variants","volume":"12","author":"C Chakraborty","year":"2021","journal-title":"mBio"},{"issue":"3","key":"pone.0333093.ref024","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":"J Cui","year":"2019","journal-title":"Nat Rev Microbiol"},{"issue":"1","key":"pone.0333093.ref025","doi-asserted-by":"crossref","first-page":"2800","DOI":"10.1038\/s41467-023-38435-3","article-title":"Virological characteristics of the SARS-CoV-2 XBB variant derived from recombination of two Omicron subvariants","volume":"14","author":"T Tamura","year":"2023","journal-title":"Nat Commun"},{"issue":"22","key":"pone.0333093.ref026","doi-asserted-by":"crossref","first-page":"2297","DOI":"10.1016\/j.scib.2021.02.012","article-title":"Evolutionary analysis and lineage designation of SARS-CoV-2 genomes","volume":"66","author":"X Tang","year":"2021","journal-title":"Sci Bull (Beijing)"},{"key":"pone.0333093.ref027","doi-asserted-by":"crossref","first-page":"199354","DOI":"10.1016\/j.virusres.2024.199354","article-title":"Structural impact of a new spike Y170W mutation detected in early emerging SARS-CoV-2 Omicron variants in France","volume":"343","author":"M Glenet","year":"2024","journal-title":"Virus Res"},{"issue":"1","key":"pone.0333093.ref028","doi-asserted-by":"crossref","first-page":"2671","DOI":"10.1038\/s41467-023-38188-z","article-title":"Convergent evolution of SARS-CoV-2 Omicron subvariants leading to the emergence of BQ.1.1 variant","volume":"14","author":"J Ito","year":"2023","journal-title":"Nat Commun"},{"issue":"3","key":"pone.0333093.ref029","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1093\/genetics\/148.3.929","article-title":"Likelihood models for detecting positively selected amino acid sites and applications to the HIV-1 envelope gene","volume":"148","author":"R Nielsen","year":"1998","journal-title":"Genetics"},{"key":"pone.0333093.ref030","unstructured":"COVID-19 Data Portal. https:\/\/www.covid19dataportal.org\/. Accessed 2025 September 5."},{"key":"pone.0333093.ref031","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkab417","article-title":"The COVID-19 Data Portal: accelerating SARS-CoV-2 and COVID-19 research through rapid open access data sharing","volume":"49","author":"PW Harrison","year":"2021","journal-title":"Nucleic Acids Res"},{"issue":"5","key":"pone.0333093.ref032","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.1093\/nar\/gkh340","article-title":"MUSCLE: multiple sequence alignment with high accuracy and high throughput","volume":"32","author":"RC Edgar","year":"2004","journal-title":"Nucleic Acids Res"},{"issue":"15","key":"pone.0333093.ref033","doi-asserted-by":"crossref","first-page":"2571","DOI":"10.1093\/bioinformatics\/btv141","article-title":"MSA-PAD: DNA multiple sequence alignment framework based on PFAM accessed domain information","volume":"31","author":"B Balech","year":"2015","journal-title":"Bioinformatics"},{"key":"pone.0333093.ref034","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/978-1-4939-7683-6_13","article-title":"DNA Multiple Sequence Alignment Guided by Protein Domains: The MSA-PAD 2.0 Method","volume":"1746","author":"B Balech","year":"2018","journal-title":"Methods Mol Biol"},{"issue":"5","key":"pone.0333093.ref035","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.1093\/molbev\/msaa015","article-title":"IQ-TREE 2: New Models and Efficient Methods for Phylogenetic Inference in the Genomic Era","volume":"37","author":"BQ Minh","year":"2020","journal-title":"Mol Biol Evol"},{"issue":"2","key":"pone.0333093.ref036","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1093\/molbev\/msx281","article-title":"UFBoot2: Improving the Ultrafast Bootstrap Approximation","volume":"35","author":"DT Hoang","year":"2018","journal-title":"Mol Biol Evol"},{"key":"pone.0333093.ref037","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkae268","article-title":"Interactive Tree of Life (iTOL) v6: recent updates to the phylogenetic tree display and annotation tool","volume":"52","author":"I Letunic","year":"2024","journal-title":"Nucleic Acids Res"},{"issue":"12","key":"pone.0333093.ref038","doi-asserted-by":"crossref","first-page":"2472","DOI":"10.1093\/molbev\/msi237","article-title":"Evaluation of an improved branch-site likelihood method for detecting positive selection at the molecular level","volume":"22","author":"J Zhang","year":"2005","journal-title":"Mol Biol Evol"},{"issue":"5","key":"pone.0333093.ref039","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1093\/molbev\/msi105","article-title":"Not so different after all: a comparison of methods for detecting amino acid sites under selection","volume":"22","author":"SL Kosakovsky Pond","year":"2005","journal-title":"Mol Biol Evol"},{"issue":"5","key":"pone.0333093.ref040","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1093\/molbev\/mst030","article-title":"FUBAR: a fast, unconstrained bayesian approximation for inferring selection","volume":"30","author":"B Murrell","year":"2013","journal-title":"Mol Biol Evol"},{"issue":"7","key":"pone.0333093.ref041","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1002764","article-title":"Detecting Individual Sites Subject to Episodic Diversifying Selection","volume":"8","author":"B Murrell","year":"2012","journal-title":"PLoS Genet"},{"key":"pone.0333093.ref042","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkx439","article-title":"SDM: a server for predicting effects of mutations on protein stability","volume":"45","author":"AP Pandurangan","year":"2017","journal-title":"Nucleic Acids Res"},{"issue":"7","key":"pone.0333093.ref043","doi-asserted-by":"crossref","first-page":"3696","DOI":"10.3390\/ijms25073696","article-title":"Properties and Mechanisms of Deletions, Insertions, and Substitutions in the Evolutionary History of SARS-CoV-2","volume":"25","author":"IB Rogozin","year":"2024","journal-title":"Int J Mol Sci"},{"key":"pone.0333093.ref044","unstructured":"COG-UK Mutation Explorer. https:\/\/sars2.cvr.gla.ac.uk\/cog-uk\/. Accessed 2025 September 5."},{"key":"pone.0333093.ref045","unstructured":"CoVEpiAb. https:\/\/pgx.zju.edu.cn\/covepiab\/. Accessed 2025 September 5."},{"issue":"8021","key":"pone.0333093.ref046","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1038\/s41586-024-07636-1","article-title":"Spike deep mutational scanning helps predict success of SARS-CoV-2 clades","volume":"631","author":"B Dadonaite","year":"2024","journal-title":"Nature"},{"issue":"2","key":"pone.0333093.ref047","article-title":"The emergence of sars-cov-2 variants of concern is driven by acceleration of the substitution rate","volume":"39","author":"JH Tay","year":"2022","journal-title":"Mol Biol Evol"},{"key":"pone.0333093.ref048","doi-asserted-by":"crossref","DOI":"10.3389\/fmolb.2022.893843","article-title":"Biochemical Characterization of SARS-CoV-2 Spike RBD Mutations and Their Impact on ACE2 Receptor Binding","volume":"9","author":"A Hoter","year":"2022","journal-title":"Front Mol Biosci"},{"key":"pone.0333093.ref049","author":"J Ai","year":"2022"},{"issue":"6506","key":"pone.0333093.ref050","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1126\/science.abd0831","article-title":"Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies","volume":"369","author":"A Baum","year":"2020","journal-title":"Science"},{"issue":"4","key":"pone.0333093.ref051","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1038\/s41591-021-01294-w","article-title":"Resistance of SARS-CoV-2 variants to neutralization by monoclonal and serum-derived polyclonal antibodies","volume":"27","author":"RE Chen","year":"2021","journal-title":"Nat Med"},{"issue":"15","key":"pone.0333093.ref052","doi-asserted-by":"crossref","DOI":"10.1016\/j.cell.2021.06.002","article-title":"The monoclonal antibody combination REGEN-COV protects against SARS-CoV-2 mutational escape in preclinical and human studies","volume":"184","author":"R Copin","year":"2021","journal-title":"Cell"},{"issue":"3","key":"pone.0333093.ref053","doi-asserted-by":"crossref","DOI":"10.1016\/j.chom.2021.02.003","article-title":"Comprehensive mapping of mutations in the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human plasma antibodies","volume":"29","author":"AJ Greaney","year":"2021","journal-title":"Cell Host Microbe"},{"issue":"9","key":"pone.0333093.ref054","doi-asserted-by":"crossref","DOI":"10.1016\/j.cell.2021.03.028","article-title":"N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2","volume":"184","author":"M McCallum","year":"2021","journal-title":"Cell"},{"issue":"6531","key":"pone.0333093.ref055","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1126\/science.abf9302","article-title":"Prospective mapping of viral mutations that escape antibodies used to treat COVID-19","volume":"371","author":"TN Starr","year":"2021","journal-title":"Science"},{"issue":"9","key":"pone.0333093.ref056","doi-asserted-by":"crossref","DOI":"10.1016\/j.cell.2021.03.029","article-title":"Neutralizing and protective human monoclonal antibodies recognizing the N-terminal domain of the SARS-CoV-2 spike protein","volume":"184","author":"N Suryadevara","year":"2021","journal-title":"Cell"},{"key":"pone.0333093.ref057","author":"Y Wang","year":"2022"},{"key":"pone.0333093.ref058","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkr363","article-title":"SDM--a server for predicting effects of mutations on protein stability and malfunction","volume":"39","author":"CL Worth","year":"2011","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"pone.0333093.ref059","doi-asserted-by":"crossref","first-page":"20274","DOI":"10.1038\/s41598-021-99827-3","article-title":"Molecular rationale for SARS-CoV-2 spike circulating mutations able to escape bamlanivimab and etesevimab monoclonal antibodies","volume":"11","author":"E Laurini","year":"2021","journal-title":"Sci Rep"},{"issue":"211","key":"pone.0333093.ref060","doi-asserted-by":"crossref","DOI":"10.1098\/rsif.2023.0614","article-title":"Predicting potential SARS-CoV-2 mutations of concern via full quantum mechanical modelling","volume":"21","author":"M Zaccaria","year":"2024","journal-title":"J R Soc Interface"},{"issue":"4","key":"pone.0333093.ref061","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1620\/tjem.250.271","article-title":"The Coronavirus Disease 2019 (COVID-19) Pandemic","volume":"250","author":"S Baloch","year":"2020","journal-title":"Tohoku J Exp Med"},{"issue":"2","key":"pone.0333093.ref062","doi-asserted-by":"crossref","first-page":"108630","DOI":"10.1016\/j.celrep.2020.108630","article-title":"D614G mutation alters SARS-CoV-2 spike conformation and enhances protease cleavage at the S1\/S2 junction","volume":"34","author":"SM-C Gobeil","year":"2021","journal-title":"Cell Reports"},{"issue":"8","key":"pone.0333093.ref063","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1056\/NEJMoa2116597","article-title":"Effect of Covid-19 Vaccination on Transmission of Alpha and Delta Variants","volume":"386","author":"DW Eyre","year":"2022","journal-title":"N Engl J Med"},{"key":"pone.0333093.ref064","author":"F Muecksch","year":"2021"},{"issue":"1","key":"pone.0333093.ref065","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1038\/s41467-024-45274-3","article-title":"Virological characteristics of the SARS-CoV-2 Omicron XBB.1.5 variant","volume":"15","author":"T Tamura","year":"2024","journal-title":"Nat Commun"},{"issue":"13","key":"pone.0333093.ref066","doi-asserted-by":"crossref","first-page":"109292","DOI":"10.1016\/j.celrep.2021.109292","article-title":"Recurrent emergence of SARS-CoV-2 spike deletion H69\/V70 and its role in the Alpha variant B.1.1.7","volume":"35","author":"B Meng","year":"2021","journal-title":"Cell Rep"},{"key":"pone.0333093.ref067","doi-asserted-by":"crossref","first-page":"2579","DOI":"10.2147\/IDR.S320658","article-title":"Detection of Representative Mutant Strains and a Case of Prolonged Infection by SARS-CoV-2 with Spike 69\/70 Deletion in Japan","volume":"14","author":"K Takano","year":"2021","journal-title":"Infect Drug Resist"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0333093","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T17:42:47Z","timestamp":1761068567000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0333093"}},"subtitle":[],"editor":[{"given":"Babatunde Olanrewaju","family":"Motayo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,10,21]]},"references-count":67,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10,21]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0333093","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,21]]}}}