Anti-diabetic drug discovery using the bioactive compounds of Momordica charantia by molecular docking and molecular dynamics analysis.

Diabetes mellitus (DM) is a multifactorial life-threatening endocrine disease characterized by abnormalities in glucose metabolism. It is a chronic metabolic disease that involves multiple enzymes such as α-amylase and α-glucosidases. Inhibition of these enzymes has been identified as a promising method for managing diabetes, and researchers are currently focusing on discovering novel α-amylase and α-glucosidase inhibitors for diabetes therapy. Hence, we have selected 12 bioactive compounds from the Momordica charantia (MC) plant and performed a virtual screening and molecular dynamics investigation to identify natural inhibitors of α-amylase and α-glucosidases. Our in silico result revealed that phytocompound Rutin showed the highest binding affinity against α-amylase (1HNY) enzymes at (-11.68 kcal/mol), followed by Karaviloside II (-9.39), Momordicoside F (-9.19), Campesterol (-9.11. While docking against α-glucosidases (4J5T), Rutin again showed the greatest binding affinity (-11.93 kcal/mol), followed by Momordicine (-9.89), and Campesterol (-8.99). Molecular dynamics (MD) simulation research is currently the gold standard for drug design and discovery. Consequently, we conducted simulations of 100 nanoseconds (ns) to assess the stability of protein-ligand complexes based on parameters like RMSD, RMSF, RG, PCA, and FEL. The significance of our findings indicates that rutin from MC might serve as an effective natural therapeutic agent for diabetes management due to its strongest binding affinities with α-amylase and α-glucosidase enzymes. Further research in animals and humans is essential to validate the efficacy of these drug molecules.Communicated by Ramaswamy H. Sarma.

Computational investigation of phytochemicals identified from medicinal plant extracts against tuberculosis.

Tuberculosis (TB) is still one of the world's most challenging infectious diseases and the emergence of drug-resistant Mycobacterium tuberculosis poses a significant threat to the treatment of TB. Identifying new medications based on local traditional remedies has become more essential. Gas Chromatography-Mass spectrometry (GC-MS) (Perkin-Elmer, MA, USA) was used to identify potential bioactive components in Solanum surattense, Piper longum, and Alpinia galanga plants sections. The fruits and rhizomes' chemical compositions were analyzed using solvents like petroleum ether, chloroform, ethyl acetate, and methanol. A total of 138 phytochemicals were identified, further categorized and finalized with 109 chemicals. The phytochemicals were docked with selected proteins (ethA, gyrB, and rpoB) using AutoDock Vina. The top complexes were selected and preceded with molecular dynamics simulation. It was found that the rpoB-sclareol complex is very stable, which means it could be further explored. The compounds were further studied for ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) properties. Sclareol has obeyed all the rules and it might be a potential chemical to treat TB.Communicated by Ramaswamy H. Sarma.

Meta-analysis of active tuberculosis gene expression ascertains host directed drug targets.

Multi-drug resistant tuberculosis still remains a major public health crisis globally. With the emergence of newer active tuberculosis disease, the requirement of prolonged treatment time and adherence to therapy till its completion necessitates the search of newer therapeutics, targeting human host factors. The current work utilized statistical meta-analysis of human gene transcriptomes of active pulmonary tuberculosis disease obtained from six public datasets. The meta-analysis resulted in the identification of 2038 significantly differentially expressed genes (DEGs) in the active tuberculosis disease. The gene ontology (GO) analysis revealed that these genes were major contributors in immune responses. The pathway enrichment analyses identified from various human canonical pathways are related to other infectious diseases. In addition, the comparison of the DEGs with the tuberculosis genome wide association study (GWAS) datasets revealed the presence of few genetic variants in their proximity. The analysis of protein interaction networks (human and Mycobacterium tuberculosis) and host directed drug-target interaction network led to new candidate drug targets for drug repurposing studies. The current work sheds light on host genes and pathways enriched in active tuberculosis disease and suggest potential drug repurposing targets for host-directed therapies.

Interaction of Host Pattern Recognition Receptors (PRRs) with Mycobacterium Tuberculosis and Ayurvedic Management of Tuberculosis: A Systemic Approach.

Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis (Mtb), infects the lungs' alveolar surfaces through aerosol droplets. At this stage, the disease progression may have many consequences, determined primarily by the reactions of the human immune system. However, one approach will be to more actively integrate the immune system, especially the pattern recognition receptor (PRR) systems of the host, which notices pathogen-associated molecular patterns (PAMPs) of Mtb. Several types of PRRs are involved in the detection of Mtb, including Toll-like receptors (TLRs), C-type lectin receptors (CLRs), Dendritic cell (DC) -specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), Mannose receptor (MR), and NOD-like receptors (NLRs) related to inflammasome activation. In this study, we focus on reviewing the Mtb pathophysiology and interaction of host PPRs with Mtb as well as adverse drug effects of anti-tuberculosis drugs (ATDs) and systematic TB treatment via Ayurvedic medicine.

Exploring genetic targets of psoriasis using genome wide association studies (GWAS) for drug repurposing.

Psoriasis is a chronic inflammatory disease causing itching in the body and pain in the joints. Currently, no permanent cure is available at a commercial level for this disease. Genome wide association studies (GWAS) provide a deeper insight that helps in better understanding this disease and further possible cure of this disease. The major goal of the present study is to identify potent genetic targets of psoriasis disease using GWAS approach and identify drugs for repurposing. The methods used include GWAS catalogue, GeneAnalytics, canSAR protein annotation tool, VarElect, Drug bank, Proteomics database, ProTox software. By exploring GWAS catalogue, 126 psoriasis associated genes (PAG) were identified. 68 genes found to be druggable were obtained from canSAR protein annotation tool. Localization results depict that maximum genes are present in cytoplasmic cellular components. The superpathways obtained from GeneAnalytics resulted in involvement of these genes in the immune system, Jak/Stat pathway, Th17 and Wnt pathways. Two genes Interleukin 13 (IL13) and POLI are Food and Drug Administration (FDA) approved targets. Small compounds for these targets were analysed for drug-likeliness, toxicity and mutagenecity properties. The FDA approved drug pandel was found to possess desirable properties. The medications used for psoriasis causes mild to severe side effects and does not work well always. Hence we propose drug repurposing strategy to use existing drugs for new therapies. Therefore, the drug pandel could be explored further and repurposed to treat psoriasis.