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

Punicalagin is the most bioactive pomegranate polyphenol with high antioxidant and free-radical scavenging activity and can potentially cure different ailments related to the cardiovascular system. The current research work was envisioned to predict the targeting efficiency of punicalagin (PG) nanoparticles to the macrophages, more specifically to bone marrow macrophages. For this, we selected mannose-decorated PLGA-punicalagin nanoparticles (Mn-PLGA-PG), and before formulating this nanocarrier in laboratory settings, we predicted the targeting efficiency of this nanocarrier by in silico analysis. The analysis proceeded with macrophage mannose receptors to be acquainted with the binding affinity and punicalagin-based nanocarrier interactions with this receptor. In silico docking studies of macrophage mannose receptors and punicalagin showed binding interactions on its surface. PG interacted with hydrogen bonds to the charged residue ASP668 and GLY666 and polar residue GLN760 of the Mn receptor. Mannose with a docking score of −5.811 Kcal/mol interacted with four hydrogen bonds and the mannose receptor of macrophage, and in PLGA, it showed a −4.334 Kcal/mol docking score. Further, the analysis proceeded with density functional theory analysis (DFT) and HOMO–LUMO analysis, followed by an extensive 100 ns molecular dynamics simulation to analyse the trajectories showing the slightest deviation and fluctuation. While analysing the ligand and protein interaction, a wonderful interaction was found among the atoms of the ligand and protein residues. This computational study confirms that this nanocarrier could be a promising lead molecule to regulate the incidence of drug-induced neutropenia. Furthermore, experimental validation is required before this can be stated with complete confidence or before human use.