Unveiling potent inhibitors for schistosomiasis through ligand-based drug design, molecular docking, molecular dynamics simulations and pharmacokinetics predictions.

Schistosomiasis is a neglected tropical disease which imposes a considerable and enduring impact on affected regions, leading to persistent morbidity, hindering child development, diminishing productivity, and imposing economic burdens. Due to the emergence of drug resistance and limited management options, there is need to develop additional effective inhibitors for schistosomiasis. In view of this, quantitative structure-activity relationship studies, molecular docking, molecular dynamics simulations, drug-likeness and pharmacokinetics predictions were applied to 39 Schistosoma mansoni Thioredoxin Glutathione Reductase (SmTGR) inhibitors. The chosen QSAR model demonstrated robust statistical parameters, including an R2 of 0.798, R2adj of 0.767, Q2cv of 0.681, LOF of 0.930, R2test of 0.776, and cR2p of 0.746, confirming its reliability. The most active derivative (compound 40) was identified as a lead candidate for the development of new potential non-covalent inhibitors through ligand-based design. Subsequently, 12 novel compounds (40a-40l) were designed with enhanced anti-schistosomiasis activity and binding affinity. Molecular docking studies revealed strong and stable interactions, including hydrogen bonding, between the designed compounds and the target receptor. Molecular dynamics simulations over 100 nanoseconds and MM-PBSA free binding energy (ΔGbind) calculations validated the stability of the two best-designed molecules. Furthermore, drug-likeness and pharmacokinetics prediction analyses affirmed the potential of these designed compounds, suggesting their promise as innovative agents for the treatment of schistosomiasis.

In-silico formulation of a next-generation polyvalent vaccine against multiple strains of monkeypox virus and other related poxviruses.

Mpox (formerly known as monkeypox) virus and some related poxviruses including smallpox virus pose a significant threat to public health, and effective prevention and treatment strategies are needed. This study utilized a reverse vaccinology approach to retrieve conserved epitopes for monkeypox virus and construct a vaccine that could provide cross-protection against related viruses with similar antigenic properties. The selected virulent proteins of monkeypox virus, MPXVgp165, and Virion core protein P4a, were subjected to epitope mapping for vaccine construction. Two vaccines were constructed using selected T cell epitopes and B cell epitopes with PADRE and human beta-defensins adjuvants conjugated in the vaccine sequence. Both constructs were found to be highly antigenic, non-allergenic, nontoxic, and soluble, suggesting their potential to generate an adequate immune response and be safe for humans. Vaccine construct 1 was selected for molecular dynamic simulation studies. The simulation studies revealed that the TLR8-vaccine complex was more stable than the TLR3-vaccine complex. The lower RMSD and RMSF values of the TLR8 bound vaccine compared to the TLR3 bound vaccine suggested better stability and consistency of hydrogen bonds. The Rg values of the vaccine chain bound to TLR8 indicated overall stability, whereas the vaccine chain bound to TLR3 showed deviations throughout the simulation. These results suggest that the constructed vaccine could be a potential preventive measure against monkeypox and related viruses however, further experimental validation is required to confirm these findings.

Antifungal plant flavonoids identified in silico with potential to control rice blast disease caused by Magnaporthe oryzae.

Rice blast disease, caused by the fungus Magnaporthe oryzae, poses a severe threat to rice production, particularly in Asia where rice is a staple food. Concerns over fungicide resistance and environmental impact have sparked interest in exploring natural fungicides as potential alternatives. This study aimed to identify highly potent natural fungicides against M. oryzae to combat rice blast disease, using advanced molecular dynamics techniques. Four key proteins (CATALASE PEROXIDASES 2, HYBRID PKS-NRPS SYNTHETASE TAS1, MANGANESE LIPOXYGENASE, and PRE-MRNA-SPLICING FACTOR CEF1) involved in M. oryzae's infection process were identified. A list of 30 plant metabolites with documented antifungal properties was compiled for evaluation as potential fungicides. Molecular docking studies revealed that 2-Coumaroylquinic acid, Myricetin, Rosmarinic Acid, and Quercetin exhibited superior binding affinities compared to reference fungicides (Azoxystrobin and Tricyclazole). High throughput molecular dynamics simulations were performed, analyzing parameters like RMSD, RMSF, Rg, SASA, hydrogen bonds, contact analysis, Gibbs free energy, and cluster analysis. The results revealed stable interactions between the selected metabolites and the target proteins, involving important hydrogen bonds and contacts. The SwissADME server analysis indicated that the metabolites possess fungicide properties, making them effective and safe fungicides with low toxicity to the environment and living beings. Additionally, bioactivity assays confirmed their biological activity as nuclear receptor ligands and enzyme inhibitors. Overall, this study offers valuable insights into potential natural fungicides for combating rice blast disease, with 2-Coumaroylquinic acid, Myricetin, Rosmarinic Acid, and Quercetin standing out as promising and environmentally friendly alternatives to conventional fungicides. These findings have significant implications for developing crop protection strategies and enhancing global food security, particularly in rice-dependent regions.

MicroRNA in Fibrotic Disorders: A Potential Target for Future Therapeutics.

Fibrotic disorders are defined by accumulating excessive extracellular matrix (ECM) components, especially collagens, in various organs, leading to tissue scarring and organ dysfunction. These conditions are associated with significant challenges in the healthcare system because of their progressive nature and limited treatment options. MicroRNAs (miRNAs) are small non-coding RNA molecules (approximately 22 nucleotides) that modulate gene expression by selectively targeting mRNAs for degradation or translational repression. MiRNAs have recently been identified as potential targets for therapeutic developments in fibrotic disorders. They play vital roles in inducing fibrotic phenotype by regulating fibroblast activation and ECM remodeling. Multiple strategies for targeting specific miRNAs in fibrotic disorders have been explored, including antisense oligonucleotides, small molecule modulators, and natural compounds. This review discussed the role of miRNAs in different fibrotic disorders, including cardiac fibrosis, liver fibrosis, kidney fibrosis, lung fibrosis, dermal fibrosis, and primary myelofibrosis, with recent advances in developing miRNA-based therapeutics.

2-[(E)-(2-carboxybenzylidene) amino] ethan ammonium-like amino acid zwitterions: crystal structure, functional studies and its molecular dynamic simulation study with drug target receptors.

The novel synthetic amino acid-like zwitterion containing imine bond ionic compound 2-[(E)-(2-carboxy benzylidene) amino] ethan ammonium salt, C10H12N2O2, was synthesized. Computational functional characterization is now being used to predict novel compounds. Here, we report on a titled combination that has been crystallizing in orthorhombic space group Pcc2 with Z = 4. The zwitterions form centrosymmetric dimers to polymeric supramolecular network via intermolecular N-H… O hydrogen bonds between the carboxylate groups and ammonium ion. The components are linked by ionic (N+-H-O-) and hydrogen bonds (N+-H-O), forming a complex three-dimensional supramolecular network. Further, molecular computational docking characterization study was performed with compound against multi-disease drug target biomolecule of anticancer target molecule of HDAC8 (PDB ID 1T69) receptor and antiviral molecular target protease (PDB ID 6LU7) to evaluate the interaction stability, conformational changes and to get insights into the natural dynamics on different timescales in solution. HighlightsThe novel zwitter ionic amino acid compound 2-[(E)-(2-carboxybenzylidene) amino] ethan ammonium salt, C10H12N2O2.The crystal structure determined for this compound illustrates the presence of intermolecular ionic N+-H-O- and N+-H-O hydrogen bonds between the carboxylate groups and ammonium ion, which influence the formation of a complex three-dimensional supramolecular polymeric network.Molecular docking studies helps to understand the conformational stability and interaction stabilityThe novel molecule can be considered for anticancer treatment.

The genome of the Black Bengal goat (Capra hircus).

OBJECTIVES: Black Bengal goat (Capra hircus), a member of the Bovidae family with the unique traits of high prolificacy, skin quality and low demand for food is the most socioeconomically significant goat breed in Bangladesh. Furthermore, the aptitude of adaptation and disease resistance capacity of it is highly notable which makes its whole genome information an area of research interest. DATA DESCRIPTION: The genomic DNA of a local (Chattogram, Bangladesh) healthy male Black Bengal goat (Capra hircus) was extracted and then sequenced. Sequencing was completed using the Illumina HiSeq 2500 sequencing platform and the draft assembly was generated using the "ARS1" genome as the reference. MAKER gene annotation pipeline was utilized to annotate 26,458 gene models. Genome completeness was assessed using BUSCO (Benchmarking Universal Single-Copy Orthologs) which showed 82.5% completeness of the assembled genome.