Objective: This study was aimed to analyze the inhibitory effect of the flavonoid class of phytochemicals present in ginger (Zingiber Officinale), garlic (Allium sativum), and curry leaf (Murrayakoenigii) against some receptors of type-2 diabetes such as human aldose reductase receptor, mitogen synthase kinase receptor, as well as dipeptidyl peptidase receptor by implementing several in silico analysis techniques. Methods: The 3D structures of the flavonoid class of phytochemicals of all the three plants were retrieved from the PubChem database in 3D SDF format and were converted to PDB format using PyMol software. These phytochemicals were subjected to in silico tools such as SwissADME,  Pre-ADMET, and iMODS web server. The PDB-IDs of the targeted receptors human aldose reductase, dipeptidyl peptidase-IV, and mitogen synthase kinase were retrieved from Protein Data Bank in PDB format. All these receptors were then prepared for docking procedure using Autodock Tools. Now, both the prepared proteins and ligands were subjected to docking analysis using Pyrex (AutodockVina). Results: Naringenin and kaempferol showed excellent docking results with the aldose reductase receptor. On the other hand, rutin showed the best docking score with dipeptidyl peptidase receptor-IV, whereas, epigallocatechin showed the best docking results with mitogen synthase kinase receptor. The ADME analysis showed that resveratrol had the best gastrointestinal absorption as well as high blood-brain barrier permeability. Conclusion: Overall, the molecular docking results when analyzed showed a good binding affinity with the targeted receptors of diabetes. The ADME analysis and molecular docking results of the phytochemicals concluded that these compounds can be used as a potential cure for treating diabetes.

Objective: Brain tumor is a formidable challenge for drug development, and drugs derived from many advanced technologies are being tested in clinical trials. Synaptosomal-associated protein of 25 kDa (SNAP25) is a membrane-binding protein in neurons and it is critical in neurotransmission for the fusion of plasma membrane and synaptic vesicle making it a prime target to address brain tumors. The SNAP-25 gene is responsible for personality disorders, schizophrenia, attention deficit, and hyperactivity disorder in human beings. It is recently discovered, that this protein is responsible for brain cancer as well. Methods: In the present research, 17 investigational and experimental anticancer drugs were selected from the PubChem and DrugBank databases to identify potential inhibitors with high stability to treat mutated SNAP25 protein. For this purpose, we have used the structure-based virtual screening technique wherein, the candidate molecules are computationally docked into the 3D structure of the biological. The docking was achieved in PyRx 0.8 software and the drugs were then ranked based on their predicted binding affinity or complementarity to the binding site. Results: Based on the ligand binding energy, the top six compounds having greater inhibitory effects towards SNAP25 were selected and then visualized with Pymol and Biovia visualizers. The compound Crenolanib has better pharmacological properties and demonstrated higher binding affinities with the target protein. Therefore, this Crenolanib docked confirmations were appraised for molecular dynamic simulations. Conclusion: The study concluded that the anticancer drug Crenolanib exerted inhibitory potential against the mutated protein SNAP-25 and therefore it can be exploited as a cancer modulator to address brain tumors.

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Several genetic variations of Severe Acute Respiratory Ryndrome coronavirus (SARS-CoV) are continuously arising due to the uncontrolled dissemination of the virus during the pandemic. Omicron (B.1.1.529), the most prevalent variation of concern, has demonstrated extraordinary proliferation and pathogenicity and has emerged as the dominant variant as it has inflicted mass casualties worldwide. Impeding the expression of 3CLpro, a coronavirus protease that is essential for digesting the RNA polyproteins, and the human angiotensin-converting enzyme 2 (ACE2) that serves as a receptor for the viral protein is identified as a competent therapeutic target. In the current study, human ACE2 and the viral 3CLpro complex was the target for the designing of novel drugs against the lethal virus. The docked complex was validated by Procheck, and the covid ligand library was investigated for its pharmacological efficacy using admetSAR 2.0. The molecular docking study was performed with the screened compounds obtained from the PubChem database against the docked protein complex. The molecular dynamics simulation study was effectuated using Desmond Schrodinger 2019.2 to assess the stability and interaction of the 3CLpro-ACE2 complex with the ligand followed by normal mode analysis. In addition to having favorable pharmacological qualities, the ligand 1-(4-fluorophenyl)-N'-(4-methylphenyl) propane-1,3-diamine exhibited the best binding affinity with the complex. Consequently, this compound can be used to develop anti-covid medications to combat complications associated with Omicron infection.

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