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Human Papilloma Viral Infection
Human papillomavirus (HPV) is the primary causative agent of cervical cancer, one of the most significant cancers affecting women worldwide, and is also implicated in anogenital and head-and-neck malignancies. HPV is a small, non-enveloped DNA virus whose oncogenic potential in high-risk types (notably HPV-16 and HPV-18) is driven chiefly by the E6 and E7 oncoproteins.
E6 promotes proteasomal degradation of the tumour suppressor p53, disabling apoptosis and DNA-damage checkpoints, while E7 binds and inactivates the retinoblastoma protein (pRb) through its zinc-finger motif. Together they disrupt the p53/pRb axis, driving uncontrolled proliferation and malignant transformation of cervical epithelial cells.
Our approach
Using structure- and ligand-based computer-aided drug design, homology modelling of full-length E7 and molecular dynamics, we have identified lead compounds, including EGCG analogues, with potential to restore p53 and pRb function and inhibit HPV-driven transformation.