Younas Saima, Nosheen Atiqa, Malik Zaryab Ikram, Hussain Nazim, Khan Muhammad Umer, Alhegaili Alaa S, Shabbir Zakria, Manzoor Sadia, Rehman Hafiz Muzzammel, Hammad Hafiz Muhammad
Centre for Applied Molecular Biology (CAMB), University of the Punjab, Lahore, Pakistan.
Institute of Molecular Biology and Biotechnology, University of Lahore, Lahore, Pakistan.
Med Oncol. 2025 Apr 7;42(5):153. doi: 10.1007/s12032-025-02711-7.
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.
宫颈癌是全球女性中第四常见的癌症，主要由高危型人乳头瘤病毒（HR-HPV）持续感染引起。人乳头瘤病毒16型（HPV-16）L1衣壳蛋白在免疫识别和病毒传播中起关键作用。本研究旨在对从巴基斯坦拉合尔收集的HR-HPV16样本中的L1基因进行分子分析，并通过计算机模拟分析确定针对L1蛋白的潜在抑制剂。使用聚合酶链反应（PCR）扩增L1基因，随后进行凝胶纯化和桑格测序。核苷酸和氨基酸序列比对用于评估变异区域。使用包括ADMET、CBDOCK 2和Maestro Schrodinger在内的计算机模拟工具来评估各种化合物与L1蛋白的不同参数。该研究在L1序列中鉴定出突变，包括V357G、V359G、S369A和C371W，这些突变可能影响HPV-16的行为和癌症发展。新刺孢菌素被确定为一种有前景的HPV16 L1衣壳蛋白抑制剂，对L1蛋白具有最高的结合能分数（-7.6千卡/摩尔），表明其具有潜在的抗病毒功效。这些突变可能会改变L1蛋白的结构完整性，潜在地影响HPV-16的感染性及其在宫颈癌进展中的作用，而虚拟筛选方法证明是一种发现具有生物学影响的化合物的经济有效方法。通过计算机模拟工具确定新刺孢菌素为潜在的HPV16 L1衣壳蛋白抑制剂，还需要进一步的体外和体内研究来证实其抗病毒功效。
