Investigation of VEGF (rs 699947) polymorphism in the progression of Rheumatoid Arthritis (RA) and in-silico nanoparticle drug delivery of potential phytochemicals to cure RA.

Mutation in the VEGF gene disturbs the production of chondrocytes and angiogenesis which are essential for cartilage health. Cytokines and chemokines produced by auto-activation of B-cells degrade cartilage. Bruton's Tyrosine Kinase (BTK) plays a crucial role in the activation of these B-cells. VEGF has a central part in angiogenesis, in the recruitment of endothelial cells, and is involved in mechanisms that result in tumour formation. The objective of this research is to investigate the potential role of VEGF polymorphism in the development of Rheumatoid Arthritis (RA) and the screening of potential natural, synthetic BTK inhibitor compounds as possible in-silico chemotherapeutic agents to control auto-activation of B-cells and cartilage degrading cytokines. In this study, it had been shown that allele A frequency was significantly higher than that of allele C in RA-positive patients as compared to controls. Hence it depicts that allele A of VEGF (rs699947) can increase the risk of RA while allele C has a protective role. The phytochemicals which showed maximum binding affinity at the inhibitory site of BTK include beta boswellic acid, tanshinone, and baicalin. These phytochemicals as BTK inhibitor give insights to use them as anti-arthritic compounds by nanoparticle drug delivery mechanism.

A reverse vaccinology approach to design an mRNA-based vaccine to provoke a robust immune response against HIV-1.

There have been substantial advances in HIV research over the past three decades, but we are still far from our goal of eliminating HIV-1 infection entirely. Numerous ever-evolving antigens are produced as a result of HIV-1's genetic variability. Developing an effective vaccination is challenging because of the structural properties of the viral envelope glycoprotein that obscure conserved receptor-binding sites and the presence of carbohydrate moieties that prevent antibodies from reaching potential epitopes. To work on an HIV-specific vaccine, this study identified 5 HIV-surface proteins, from the literature, to screen potential epitopes and construct an mRNA vaccine. A wide range of immunological-informatics techniques were utilized to develop a construct that efficiently stimulated cellular and humoral immune responses. The vaccine was produced with 31 epitopes, a TLR4 agonist termed RpfE that acts as an adjuvant, secretion boosters, subcellular trafficking structures, and linkers. It was determined that this suggested vaccine would cover 98.9 percent of the population, making it widely available. We, furthermore, carried out an immunological simulation of the vaccine illustrating the active and stable responses from innate and adaptive immune cells, the memory cells remained active for up to 350 days after vaccine injection, whereas the antigen was excreted from the body within 24 hours. Docking performed with TLR-4 and TLR-3 showed significant interaction with -11.9kcal/mol and -18.2kcal/mol-1 respectively. Molecular dynamics simulations further validated the vaccine's stability, with a dissociation constant of 1.7E-11 for the TLR3-vaccine complex and 5.8E-11 for the TLR4-vaccine complex. Lastly, codon optimization was carried out to guarantee that the designed mRNA construct would be translated into the host successfully. This vaccine adaptation, if tested in-vitro, would be efficacious and potent as predicted.

Chain-Engineering-Based De Novo Drug Design against MPXVgp169 Virulent Protein of Monkeypox Virus: A Molecular Modification Approach.

The unexpected appearance of the monkeypox virus and the extensive geographic dispersal of cases have prompted researchers to concentrate on potential therapeutic approaches. In addition to its vaccine build techniques, there should be some multiple integrated antiviral active compounds because of the MPV (monkeypox virus) outbreak in 2022. This study offers a computational engineering-based de novo drug discovery mediated by random antiviral active compounds that were screened against the virulent protein MPXVgp169, as one of the key players directing the pathogenesis of the virus. The screening of these candidates was supported by the use of 72 antiviral active compounds. The top candidate with the lowest binding affinity was selected for the engineering of chains or atoms. Literature assisted to identify toxic chains or atoms that were impeding the stability and effectiveness of antiviral compounds to modify them for enhanced efficacy. With a binding affinity of -9.4 Kcal/mol after chain, the lipophilicity of 0.41, the water solubility of 2.51 as soluble, and synthetic accessibility of 6.6, chain-engineered dolutegravir was one of the best active compounds, as proved by the computational engineering analysis. This study will revolutionize the era of drug engineering as a potential therapeutic strategy for monkeypox infection.