Genetic analysis of HPV-16 L1 gene mutations and computational screening of therapeutic inhibitors for cervical cancer treatment

Cervical cancer, the fourth most common carcinoma in women worldwide, is predominantly caused by persistent infection with high risk human papillomavirus (HR-HPV). The human papillomavirus type 16 (HPV-16) L1 capsid protein plays a crucial role in immune recognition and viral dissemination. This study aims to conduct molecular analysis of the L1 gene from HR-HPV16 samples collected in Lahore, Pakistan, and to identify potential inhibitors against the L1 protein through in-silico analysis. The L1 gene was amplified using PCR (Polymerase Chain Reaction), followed by gel purification and Sanger sequencing. Nucleotide and amino acid sequence alignments were used to assess variant regions. In silico tools, including ADMET, CB DOCK 2 and Maestro Schrodinger, were employed to evaluate different parameters of various compounds with L1 protein. The study identified mutations in L1 sequences, including V357G, V359G, S369A, AND C371W, which could impact HPV-16 behavior and cancer development. Neoechinulin was identified as a promising HPV16 L1 capsid protein inhibitor with the highest binding energy score (-7.6 kcal/mol) against the L1 protein, suggesting potential antiviral efficacy. These mutations may alter the structural integrity of the L1 protein, potentially influencing HPV-16 infectivity and its role in cervical cancer progression, while virtual screening method demonstrated a cost- effective approach for discovering biologically impactful compounds. Neoechinulin identified as a potential HPV16 L1 capsid protein inhibitor through In Silico tools, further in vitro and in vivo studies are needed to confirm its antiviral efficacy.