In-silico analysis reveals Quinic acid as a multitargeted inhibitor against Cervical Cancer

• Published in: Journal of biomolecular structure & dynamics Vol. 41; no. 19; pp. 9770 - 9786
• Main Authors: Ahmad, Shaban, Sayeed, Salwa, Bano, Nagmi, Sheikh, Kayenat, Raza, Khalid
• Format: Journal Article
• Language: English
• Published: Taylor & Francis 24.11.2023
• Subjects: enrichment analysis; Human papillomavirus; molecular docking; molecular dynamics simulation; Quinic acid; signaling pathway
• ISSN: 0739-1102; 1538-0254
• DOI: 10.1080/07391102.2022.2146202

The cervix is the lowermost part of the uterus that connects to the vagina, and cervical cancer is a malignant cervix tumour. One of this cancer's most important risk factors is HPV infection. In the approach to finding an effective treatment for this disease, various works have been done around genomics and drug discovery. Finding the major altered genes was one of the most significant studies completed in the field of cervical cancer by TCGA (The Cancer Genome Atlas), and these genes are TGFBR2, MED1, ERBB3, CASP8, and HLA-A. The greatest genomic alterations were found in the PI3K/MAPK and TGF-Beta signalling pathways, suggesting that numerous therapeutic targets may come from these pathways in the future. We, therefore, conducted a combined enrichment analysis of genes gathered from various works of literature for this study. The final six key genes from the list were obtained after enrichment analysis using GO, KEGG, and Reactome methods. The six proteins against the identified genes were then subjected to a docking-based screening against a library of 6,87,843 prepared natural compounds from the ZINC15 database. The most stable compound was subsequently discovered through virtual screening to be the natural substance Quinic acid, which also had the highest binding affinity for all six proteins and a better docking score. To examine their stability, the study was extended to MM/GBSA and MD simulations on the six docked proteins, and comparative docking-based calculations led us to identify the Quinic Acid as a multitargeted compound. The overall deviation of the compound was less than 2 Å for all the complexes considered best for the biological molecules, and the simulation interaction analysis reveals a huge web of interaction during the simulation. Communicated by Ramaswamy H. Sarma