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

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.

Potential Therapeutic Implications of Caffeic Acid in Cancer Signaling: Past, Present, and Future.

Caffeic acid (CA) has been present in many herbs, vegetables, and fruits. CA is a bioactive compound and exhibits various health advantages that are linked with its anti-oxidant functions and implicated in the therapy and prevention of disease progression of inflammatory diseases and cancer. The anti-tumor action of CA is attributed to its pro-oxidant and anti-oxidant properties. CA's mechanism of action involves preventing reactive oxygen species formation, diminishing the angiogenesis of cancer cells, enhancing the tumor cells' DNA oxidation, and repressing MMP-2 and MMP-9. CA and its derivatives have been reported to exhibit anti-carcinogenic properties against many cancer types. CA has indicated low intestinal absorption, low oral bioavailability in rats, and pitiable permeability across Caco-2 cells. In the present review, we have illustrated CA's therapeutic potential, pharmacokinetics, and characteristics. The pharmacological effects of CA, the emphasis on in vitro and in vivo studies, and the existing challenges and prospects of CA for cancer treatment and prevention are discussed in this review.

In silico approach to understand the epigenetic mechanism of SARS-CoV-2 and its impact on the environment.

The novel coronavirus (2019-nCoV) has led to the apex pandemic in 2020, responsible for the recent sequential spread. The 2019-nCoV has been discerned to be a Beta-BAT-SARS-CoV-2 lineage. The gene ontology (GO) identifies the virus to be localized in the Golgi apparatus with a vital molecular function of binding and viral progression. The source organism is almost all bats, further suggesting that the host of this virus is bat rather than civets or snakes, and has motifs which are perfect matches to various human and mouse genomic motifs such as-zinc fingers, DNA-binding domains, and basic helix-loop-helix factors. It has basic clusters of orthologs (COGs)-Superfamily I DNA and RNA helicases and helicase subunits and Predicted phosphatase homologous to the C-terminal domain of histone macroH2A1 respectively hinting at the epigenetic alterations which could be the reason behind the "novelty" the virus. Our study discerns that the SARS-CoV-2 endorses the epigenetic mechanism essential for its replication and reproduction in the host organism. Furthermore, we identified six non-toxic disinfectants with higher pharmacokinetics and pharmacodynamics properties, namely Quaternary Ammonium, Octanoic acid, Citric acid, Phenolics, 1,2-Hexanediol, and Thymol, that bind to lyases, nuclear receptors, fatty acids binding family, enzymes, and family AG protein-coupled receptors indicating that they target the nucleocapsid (N) protein, envelope (E) protein, membranous proteins of the novel coronavirus, thus, killing it from the surfaces when sprayed and are not harmful to the biological environment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13337-021-00655-w.