{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T17:53:42Z","timestamp":1791568422945,"version":"4.3.4"},"reference-count":89,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"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>Head and neck squamous cell carcinoma is increasingly being reported worldwide, and a major contributing factor is the incidence of human papillomavirus infections. The viral infection activates proto-oncogenes and signalling mechanisms aiding in tumorigenesis. An efficient way to block the virus-induced carcinogenesis is to identify a common medicament that can effectively inhibit the viral and host proteins. In the present study, HNSCC transcriptomic profiles and HPV genes involved in host-pathogen interactions were retrieved. The overexpressed HNSCC genes were further considered for host-pathogen and protein-protein interaction network analyses. Validated viral and host hub-genes were then docked with antiviral peptides with anticancer activities and subjected to simulation studies. Interactome analyses identified CDK1, CCNA2, CAV1, BRCA1, TERT and EGFR as host hub-genes, while E5_HPV16, E6_HPV33, E7_HPV16, 18 and 33 were screened as viral hub-genes. Functional, clinical, mutational and survival analyses filtered CDK1, CCNA2 and CAV1 as potential host therapeutic targets. Four antiviral-anticancer peptides were filtered after physico-chemical screening, which were docked with the host and viral proteins. Among them, peptide 4 (AP02569) was identified to have a high average binding affinity with an average binding energy of \u22121048.01 kcal\/mol across all targets. The molecular dynamics simulations of peptide 4 demonstrated the overall stability among the docked complexes of all targets. It further indicated that peptide 4 had minimal fluctuation across all the docked complexes, and MM-GBSA analysis showed that peptide 4 was able to form energetically stable complexes with all target proteins. Our findings suggest that dual-functional antiviral and anticancer compounds can be potent therapeutic interventions for viral-led carcinogenesis in head and neck cancer.<\/jats:p>","DOI":"10.1371\/journal.pone.0359513","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T17:23:56Z","timestamp":1791566636000},"page":"e0359513","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["A dual-functional antiviral and anticancer peptide to target intricate host-pathogen interacting proteins of human papillomavirus associated with head and neck cancer"],"prefix":"10.1371","volume":"21","author":[{"given":"Gayathri","family":"Ashok","sequence":"first","affiliation":[{"name":"School of Biosciences and Technology (SBST), Vellore Institute of Technology (VIT)","place":["Vellore, Tamil Nadu, India"],"department":["Department of Bio-Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soumyadip","family":"Ghosh","sequence":"additional","affiliation":[{"name":"School of Biosciences and Technology (SBST), Vellore Institute of Technology (VIT)","place":["Vellore, Tamil Nadu, India"],"department":["Department of Bio-Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2056-4750","authenticated-orcid":true,"given":"Sanandita","family":"Sengupta","sequence":"additional","affiliation":[{"name":"SBST, VIT","place":["Vellore, Tamil Nadu, India"],"department":["Department of Bio-Medical Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bikramjit","family":"Bhattacharya","sequence":"additional","affiliation":[{"name":"SBST, VIT","place":["Vellore, Tamil Nadu, India"],"department":["Department of Bio-Medical Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pratiksha","family":"Jana","sequence":"additional","affiliation":[{"name":"SBST, VIT","place":["Vellore, Tamil Nadu, India"],"department":["Department of Bio-Medical Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Livingstone","sequence":"additional","affiliation":[{"name":"School of Sports and Health Sciences, Cardiff Metropolitan University","place":["Cardiff, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4800-329X","authenticated-orcid":true,"given":"Sudha","family":"Ramaiah","sequence":"additional","affiliation":[{"name":"School of Biosciences and Technology (SBST), Vellore Institute of Technology (VIT)","place":["Vellore, Tamil Nadu, India"],"department":["Department of Bio-Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anand","family":"Anbarasu","sequence":"additional","affiliation":[{"name":"SBST, VIT","place":["Vellore, Tamil Nadu, India"],"department":["Department of Biotechnology"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,10,9]]},"reference":[{"issue":"3","key":"pone.0359513.ref001","first-page":"209","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"H Sung","year":"2021","journal-title":"CA Cancer J Clin"},{"issue":"1","key":"pone.0359513.ref002","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1002\/hed.27900","article-title":"Camera\u2010based near\u2010infrared autofluorescence versus visual identification in total thyroidectomy for parathyroid function preservation: Systematic review and meta\u2010analysis of randomized clinical trials","volume":"47","author":"L Canali","year":"2025","journal-title":"Head Neck"},{"issue":"6","key":"pone.0359513.ref003","article-title":"Advances in human papillomavirus detection and molecular understanding in head and neck cancers: Implications for clinical management","volume":"96","author":"NH Tran","year":"2024","journal-title":"J Med Virol"},{"issue":"1","key":"pone.0359513.ref004","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1056\/NEJMra1715715","article-title":"Head and neck cancer. 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