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Novel coronavirus (CoV) is the primary etiological virus responsible for the pandemic that started in Wuhan in 2019–2020.

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Neurodegenerative disorders are due to excessive neuronal apoptosis and the caspase-3 plays a key role in the apoptotic pathway. The caspase-3 inhibition may be a validated therapeutic approach for neurodegenerative disorders and an interesting target for molecular modeling studies using both Ligand and structure based approaches. In view of the above we have generated the Ligand based pharmacophore model using the Discovery studio 2.0 software. In addition to this a structure based approach has been used to validate the developed pharmacophoric features to gain a deeper insight into its molecular recognition process. This validated pharmacophore and the docking model was then implemented as a query for pharmacophore based virtual screening to prioritize the probable hits for the Caspase-3. Two ligands, ZINC12405015 and ZINC12405043 were finally selected on the basis of their fit values and docking scores. This study also reveals the important amino acids viz. His-121, Ser-205, Arg-207 which were found to be playing crucial role in the binding of the selected compounds within the active site of caspase-3.

The synthesis and SAR studies of 10 new chemical entities (NCEs) that have shown BMP-2 stimulation and osteoblast differentiation are reported. Among these, 2-((1-(benzyl(2-hydroxy-2-phenylethyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamoyl)benzoic acid (11) was the most effective while its analogue 13 also showed good activity in inducing osteoblast BMP-2 production. Compound 11 induced osteoblast differentiation in vitro, and this effect was abrogated by a physiological BMP-2 inhibitor, noggin. It also exhibited dose dependent increase in nascent bone formation (2.16- and 3.12-fold more than the control at 1 and 5 mg/kg dose, respectively) at the fracture site in rats. At the maximum osteogenic concentration, compound 11 significantly inhibited osteoblastic proteosomal activity. This compound was safe, as it had no effect on BMP synthesis in cardiovascular tissue.

A pharmacophore model has been developed using diverse classes of epidermal growth factor receptor (EGFR) tyrosine kinase (TK) inhibitors useful in the treatment of human tumours. Among the top 10 generated hypotheses, the second hypothesis, with one hydrogen bond acceptor, one ring aromatic and three hydrophobic features, was found to be the best on the basis of Cat Scramble validation as well as test set prediction (r(training) = 0.89, r(test) = 0.82). The model also maps well to the external test set molecules as well as clinically active molecules and corroborates the docking studies. Finally, 10 hits were identified as potential leads after virtual screening of ZINC database for EGFR TK inhibition. The study may facilitate the designing and discovery of novel EGFR TK inhibitors.