In view of the potential of traditional plant-based remedies (or phytomedicines) in the management of COVID-19, the present investigation was aimed at finding novel anti-SARS-CoV-2 molecules by in silico screening of bioactive phytochemicals (database) using computational methods and drug repurposing approach. A total of 160 compounds belonging to various phytochemical classes (flavonoids, limonoids, saponins, triterpenoids, steroids etc.) were selected (as initial hits) and screened against three specific therapeutic targets (Mpro/ 3CLpro, PLpro and RdRp) of SARS-CoV-2 by docking, molecular dynamics simulation and drug-likeness/ADMET studies. From our studies, six phytochemicals were identified as notable ant-SARS-CoV-2 agents (best hit molecules) with promising inhibitory effects effective against protease (Mpro and PLpro) and polymerase (RdRp) enzymes. These compounds are namely, ginsenoside Rg2, saikosaponin A, somniferine, betulinic acid, soyasapogenol C and azadirachtin A. On the basis of binding modes and dynamics studies of protein-ligand intercations, ginsenoside Rg2, saikosaponin A, somniferine were found to be the most potent ( in silico ) inhibitors potentially active against Mpro, PLpro and RdRp, respectively. The present investigation can be directed towards further experimental studies in order to confirm the anti-SARS-CoV-2 efficacy along with toxicities of identified phytomolecules.

No abstract

Diabetic retinopathy is one of the worst complications of diabetes and it is treated by invasive method. We prepared a surface modified poly (D, L-lactide-co-glycolide) i.e. PLGA nanoparticles for delivery of pioglitazone-a peroxisome proliferator-activated receptor-gamma agonist to posterior segment of the eye by topical administration. The present study investigated two grades of PLGA viz. 75:25 and 50:50. Surface modification was performed using polysorbate 80. Nanoparticles were prepared by single emulsion solvent evaporation method and optimized by using 3-factor 3-level Box-Behnken statistical design. Mean particle size, PDI and entrapment efficiency for optimized batch of PLGA 75:25 was found to be 163.23 nm, 0.286 and 91%, whereas; for PLGA 50:50 it was 171.7 nm, 0.280 and 93% respectively. DSC confirms the molecular dispersion of drug in polymer. In vitro release study showed biphasic drug release pattern with 58.48 ± 1.38% and 74.17 ± 1.38% cumulative drug release by PLGA 75:25 and 50:50 nanoparticles at the end of 10h. The release profile of pioglitazone from nanoparticles appeared to fit best with Higuchi model. In vivo study on rat showed dose dependent reduction in vascular endothelial growth factor concentration in vitreous fluid. The study reveals significance of peroxisome proliferator-activated receptor-gamma in management of diabetic retinopathy.

No abstract

No abstract