Design of a Structurally Novel Multipotent Drug Candidate by the Scaffold Architecture Technique for ACE-II, NSP15, and Mpro Protein Inhibition: Identification and Isolation of a Natural Product to Prevent the Severity of Future Variants of Covid 19 and a Colorectal Anticancer Drug.

Scaffold architecture in the sectors of biotechnology and drug discovery research include scaffold hopping and molecular modelling techniques and helps in searching for potential drug candidates containing different core structures using computer-based software, which greatly aids medicinal and pharmaceutical chemistry. Going ahead, the computational method of scaffold architecture is thought to produce new scaffolds, and the method is capable of helping search engines toward producing new scaffolds that are likely to represent potent compounds with high therapeutic applications, which is a possibility in this case as well. Here we probate a different interactive design by natural product hopping, molecular modelling, pharmacophore modelling, modification, and combination of the phytoconstituents present in different medicinal plants for developing a pharmacophore-guided good drug candidate for the variants of SARS-CoV-2 or Covid 19. In the modern era, these approaches are carried out at every level of development of scaffold queries, which are increasingly summarized from chemical structures. In this context, we report on a successfully designed drug-like candidate having a high-binding-affinity "compound SLP" by understanding the relationships between the compounds' pharmacophores, scaffold functional groups, and biological activities beyond their individual applications that abide by Lipinski's rule of five, Ghose rule, Veber rule etc. The new scaffold generated by altering the core of the known phyto-compounds holds a good predicted ADMET profile and is examined with iMODS server to check the molecular dynamics simulation with normal mode analysis (NMA). The scaffold's three-dimensional (3D) structure yields a searchable natural product koenimbine from a conformer database having good ADMET property and high availability in spice Murraya koenigii leaves. M. koenigii leaves are easily available in the market, and might ensure the immunity, good health, and well-being of people if affected with any of the variants of Covid 19. The cell viability studies of koenimbine on murine colorectal carcinoma cell line (CT-26) showed no toxicity on normal mice lymphocyte cells (MLCs). The anticancer mechanism of koenimbine was displayed by its enhanced capacity to produce intercellular reactive oxygen species (ROS) in the colorectal carcinoma cell line.

Bioinformatics and Network Pharmacology of the First Crystal Structured Clerodin: Anticancer and Antioxidant Potential against Human Breast Carcinoma Cell.

Clerodin was isolated from the medicinal plant Clerodendrum infortunatum, and CSD search showed the first crystal structure of clerodin by a single-crystal X-ray diffraction study. We checked its binding potential with target proteins by docking and conducted network pharmacology analysis, ADMET analysis, in silico pathway analysis, normal mode analysis (NMA), and cytotoxic activity studies to evaluate clerodin as a potential anticancer agent. The cell viability studies of clerodin on the human breast carcinoma cell line (MCF-7) showed toxicity on MCF-7 cells but no toxicity toward normal human lymphocyte cells (HLCs). The anticancer mechanism of clerodin was validated by its enhanced capacity to produce intracellular reactive oxygen species (ROS) and to lower the reduced glutathione content in MCF-7 cells.

Complexity of chromosomal rearrangements in Down syndrome leukemia.

Reports on imbalanced HSA21 gene expression and chromosomal rearrangements on leukemogenesis, drug sensitivity, and treatment outcome of leukemia in Down syndrome (DS) are limited. DS has been recognized as one of the most common leukemia-predisposing syndromes with unique clinical features, significant differences in treatment outcome and treatment-related toxicity profiles. Acute myeloid leukemia (AML), especially acute megakaryocytic leukemia, is reported with high cure rates presenting 80%-100% event-free survivals (EFSs); however, acute lymphoid leukemia indicates a worse prognosis in DS patients compared to non-DS children. Complex rearrangements are responsible for poor-to-very poor prognosis in all cases, irrespective of genetic predisposition or type of hematopoietic subunits affected. We report a 2-year-old female DS diagnosed with acute erythroleukemia (French-American-British: AML-M6) with highly complex chromosomal rearrangements in the bone marrow with 39 chromosomes. Parental consanguinity and genetic predisposition might be responsible for origin of multiple clones. Genetic instability and heterogeneity of complex clonal developments might cause poor prognosis. The case is a rare one with acute erythroleukemia in DS patient where too many rearrangements had masked identification of three 21s.