Computational and Pharmacological Evaluation of Capsaicin-Mediated Inhibition of HPV 16 E6 and E7 Oncoproteins: Molecular Mechanisms and Implications for Cervical Cancer Therapy

Cervical cancer remains a significant global health challenge, ranking as the fourth most common cancer among women. The primary causative agents, Human papillomavirus (HPV) strains 16 and 18, are well-known for their role in cervical carcinogenesis, primarily through the actions of the E6 and E7 oncoproteins. This study aimed to identify a natural compound capable of inhibiting both E6 and E7 oncoprotein activities, thereby offering a potential therapeutic approach using a single agent. This study also comprises an extensive in silico analysis with molecular docking studies by AutoDock Vina and Schrodinger Maestro to analyse the binding affinity, hydrogen bonds interactions of selected compounds against HPV 16 E6 &E7 proteins. GROMACS package and iMODS server was used to perform molecular dynamics simulations of protein-ligand complexes to elucidate stability of the ligands around the receptor at different time points. SwissADME was utilized for the prediction of pharmacokinetic properties while PROTOX-II helped in predicting toxicological data Capsaicin emerged as the most promising candidate, exhibiting binding energies of -7.3 kcal/mol and -5.6 kcal/mol against the HPV 16 E6 and E7 proteins, respectively. Notably, Capsaicin formed a single hydrogen bond with each oncoprotein, indicating a strong and specific interaction. The compound also demonstrated a favourable pharmacokinetic profile, with no violations of drug-likeness rules, and was classified as Toxicity Class 4, suggesting a moderate safety profile. These results, thus branding Capsaicin as a promising lead compound for further investigations in cervical cancer therapy that deserves documentation through well-equipped wet lab experiments followed by clinical studies.