An immuno-informatics approach for annotation of hypothetical proteins and multi-epitope vaccine designed against the Mpox virus.

A worrying new outbreak of Monkeypox (Mpox) in humans is caused by the Mpox virus (MpoxV). The pathogen has roughly 28 hypothetical proteins of unknown structure, function, and pathogenicity. Using reliable bioinformatics tools, we attempted to analyze the MpoxV genome, identify the role of hypothetical proteins (HPs), and design a potential candidate vaccine. Out of 28, we identified seven hypothetical proteins using multi-server validation with high confidence for the occurrence of conserved domains. Their physical, chemical, and functional characterizations, including molecular weight, theoretical isoelectric point, 3D structures, GRAVY value, subcellular localization, functional motifs, antigenicity, and virulence factors, were performed. We predicted possible cytotoxic T cell (CTL), helper T cell (HTL) and linear and conformational B cell epitopes, which were combined in a 219 amino acid multiepitope vaccine with human ß defensin as a linker. This multi-epitopic vaccine was structurally modelled and docked with toll-like receptor-3 (TLR-3). The dynamical stability of the vaccine-TLR-3 docked complexes exhibited stable interactions based on RMSD and RMSF tests. Additionally, the modelled vaccine was cloned in-silico in an E. coli host to check the appropriate expression of the final vaccine built. Our results might conform to an immunogenic and safe vaccine, which would require further experimental validation.Communicated by Ramaswamy H. Sarma.

Oncoinformatic screening of the gene clusters involved in the HER2-positive breast cancer formation along with the in silico pharmacodynamic profiling of selective long-chain omega-3 fatty acids as the metastatic antagonists.

The HER2-positive patients occupy ~ 30% of the total breast cancer patients globally where no prevalent drugs are available to mitigate the frequent metastasis clinically except lapatinib and neratinib. This scarcity reinforced researchers' quest for new medications where natural substances are significantly considered. Valuing the aforementioned issues, this research aimed to study the ERBB2-mediated string networks that work behind the HER2-positive breast cancer formation regarding co-expression, gene regulation, GAMA-receptor-signaling pathway, cellular polarization, and signal inhibition. Following the overexpression, promotor methylation, and survivability profiles of ERBB2, the super docking position of HER2 was identified using the quantum tunneling algorithm. Supramolecular docking was conducted to study the target specificity of EPA and DHA fatty acids followed by a comprehensive molecular dynamic simulation (100 ns) to reveal the RMSD, RMSF, Rg, SASA, H-bonds, and MM/GBSA values. Finally, potential drug targets for EPA and DHA in breast cancer were constructed to determine the drug-protein interactions (DPI) at metabolic stages. Considering the values resulting from the combinational models of the oncoinformatic, pharmacodynamic, and metabolic parameters, long-chain omega-3 fatty acids like EPA and DHA can be considered as potential-targeted therapeutics for HER2-positive breast cancer treatment.

Bidirectional promoters: an enigmatic genome architecture and their roles in cancers.

Bidirectional promoters are the transcription regulatory regions of genes positioned head-to-head on opposite strands. Specific sequence signals, chromatin modifications and three-dimensional structures of the transcription site facilitate the unconventional yet tightly regulated transcription proceeding in both directions from these promoters. Mutations or aberrant epigenetic changes can lead to abnormal enhanced or reduced expression from either of the bidirectionally transcribed genes resulting in tumorigenesis. Moreover, bidirectionally transcribed genes might also contribute towards the immune regulation in tumor microenvironment. In this review, we aimed to expound the characteristic features of bidirectional promoters alongside their transcriptional regulations, and ultimately, the association of these enigmatic genomic elements in different cancers.