A dual-functional antiviral and anticancer peptide to target intricate host-pathogen interacting proteins of human papillomavirus associated with head and neck cancer
4 affiliations
- 1Department of Bio-Sciences, School of Biosciences and Technology (SBST), Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, India
- 2Department of Bio-Medical Sciences, SBST, VIT, Vellore, Tamil Nadu, India
- 3School of Sports and Health Sciences, Cardiff Metropolitan University, Cardiff, United Kingdom
- 4Department of Biotechnology, SBST, VIT, Vellore, Tamil Nadu, India
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.
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BibTeX
@article{ashok2026dualfunctional,
title = {{A dual-functional antiviral and anticancer peptide to target intricate host-pathogen interacting proteins of human papillomavirus associated with head and neck cancer}},
author = {Gayathri Ashok and Soumyadip Ghosh and Sanandita Sengupta and Bikramjit Bhattacharya and Pratiksha Jana and Paul Livingstone and Sudha Ramaiah and Anand Anbarasu},
journal = {PLOS One},
year = {2026},
month = oct,
doi = {10.1371/journal.pone.0359513},
url = {https://doi.org/10.1371/journal.pone.0359513},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - A dual-functional antiviral and anticancer peptide to target intricate host-pathogen interacting proteins of human papillomavirus associated with head and neck cancer
AU - Gayathri Ashok
AU - Soumyadip Ghosh
AU - Sanandita Sengupta
AU - Bikramjit Bhattacharya
AU - Pratiksha Jana
AU - Paul Livingstone
AU - Sudha Ramaiah
AU - Anand Anbarasu
PY - 2026
DA - 2026/10/09
JO - PLOS One
DO - 10.1371/journal.pone.0359513
UR - https://doi.org/10.1371/journal.pone.0359513
AB - 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.
SN - 1932-6203
ER -