Exploring computational approaches to design mRNA Vaccine against vaccinia and Mpox viruses.

BACKGROUND: Messenger RNA (mRNA) vaccines emerged as a powerful tool in the fight against infections. Unlike traditional vaccines, this unique type of vaccine elicits robust and persistent innate and humoral immune response with a unique host cell-mediated pathogen gene expression and antigen presentation. METHODS: This offers a novel approach to combat poxviridae infections. From the genome of vaccinia and Mpox viruses, three key genes (E8L, E7R, and H3L) responsible for virus attachment and virulence were selected and employed for designing the candidate mRNA vaccine against vaccinia and Mpox viral infection. Various bioinformatics tools were employed to generate (B cell, CTL, and HTL) epitopes, of which 28 antigenic and immunogenic epitopes were selected and are linked to form the mRNA vaccine construct. Additional components, including a 5' cap, 5' UTR, adjuvant, 3' UTR, and poly(A) tail, were incorporated to enhance stability and effectiveness. Safety measures such as testing for human homology and in silico immune simulations were implemented to avoid autoimmunity and to mimics the immune response of human host to the designed mRNA vaccine, respectively. The mRNA vaccine's binding affinity was evaluated by docking it with TLR-2, TLR-3, TLR-4, and TLR-9 receptors which are subsequently followed by molecular dynamics simulations for the highest binding one to predict the stability of the binding complex. RESULTS: With a 73% population coverage, the mRNA vaccine looks promising, boasting a molecular weight of 198 kDa and a molecular formula of C8901H13609N2431O2611S48 and it is said to be antigenic, nontoxic and nonallergic, making it safe and effective in preventing infections with Mpox and vaccinia viruses, in comparison with other insilico-designed vaccine for vaccinia and Mpox viruses. CONCLUSIONS: However, further validation through in vivo and in vitro techniques is underway to fully assess its potential.

Advancements in Predictive Microbiology: Integrating New Technologies for Efficient Food Safety Models.

Predictive microbiology is a rapidly evolving field that has gained significant interest over the years due to its diverse application in food safety. Predictive models are widely used in food microbiology to estimate the growth of microorganisms in food products. These models represent the dynamic interactions between intrinsic and extrinsic food factors as mathematical equations and then apply these data to predict shelf life, spoilage, and microbial risk assessment. Due to their ability to predict the microbial risk, these tools are also integrated into hazard analysis critical control point (HACCP) protocols. However, like most new technologies, several limitations have been linked to their use. Predictive models have been found incapable of modeling the intricate microbial interactions in food colonized by different bacteria populations under dynamic environmental conditions. To address this issue, researchers are integrating several new technologies into predictive models to improve efficiency and accuracy. Increasingly, newer technologies such as whole genome sequencing (WGS), metagenomics, artificial intelligence, and machine learning are being rapidly adopted into newer-generation models. This has facilitated the development of devices based on robotics, the Internet of Things, and time-temperature indicators that are being incorporated into food processing both domestically and industrially globally. This study reviewed current research on predictive models, limitations, challenges, and newer technologies being integrated into developing more efficient models. Machine learning algorithms commonly employed in predictive modeling are discussed with emphasis on their application in research and industry and their advantages over traditional models.

An in-silico analysis of OGT gene association with diabetes mellitus.

O-GlcNAcylation is a nutrient-sensing post-translational modification process. This cycling process involves two primary proteins: the O-linked N-acetylglucosamine transferase (OGT) catalysing the addition, and the glycoside hydrolase OGA (O-GlcNAcase) catalysing the removal of the O-GlCNAc moiety on nucleocytoplasmic proteins. This process is necessary for various critical cellular functions. The O-linked N-acetylglucosamine transferase (OGT) gene produces the OGT protein. Several studies have shown the overexpression of this protein to have biological implications in metabolic diseases like cancer and diabetes mellitus (DM). This study retrieved 159 SNPs with clinical significance from the SNPs database. We probed the functional effects, stability profile, and evolutionary conservation of these to determine their fit for this research. We then identified 7 SNPs (G103R, N196K, Y228H, R250C, G341V, L367F, and C845S) with predicted deleterious effects across the four tools used (PhD-SNPs, SNPs&Go, PROVEAN, and PolyPhen2). Proceeding with this, we used ROBETTA, a homology modelling tool, to model the proteins with these point mutations and carried out a structural bioinformatics method- molecular docking- using the Glide model of the Schrodinger Maestro suite. We used a previously reported inhibitor of OGT, OSMI-1, as the ligand for these mutated protein models. As a result, very good binding affinities and interactions were observed between this ligand and the active site residues within 4Å of OGT. We conclude that these mutation points may be used for further downstream analysis as drug targets for treating diabetes mellitus.