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

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.