A dual-functional antiviral and anticancer peptide to target intricate host-pathogen interacting proteins of human papillomavirus associated with head and neck cancer.

Authors

Gayathri Ashok, Soumyadip Ghosh, Sanandita Sengupta, Bikramjit Bhattacharya, Pratiksha Jana, Paul Livingstone, Sudha Ramaiah, Anand Anbarasu

Published in

PloS one. Volume 21. Issue 10. Pages e0359513. Epub Oct 09, 2026.

Abstract

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 -1048.01 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.

PMID:
42853814
Bibliographic data and abstract were imported from PubMed on 10 Oct 2026.

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