Unravelling high-affinity binding compounds towards transmembrane protease serine 2 enzyme in treating SARS-CoV-2 infection using molecular modelling and docking studies.

The coronavirus disease-19 (COVID-19) outbreak that is caused by a highly contagious severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become a zoonotic pandemic, with approximately 24.5 million positive cases and 8.3 lakhs deaths globally. The lack of effective drugs or vaccine provoked the research for drug candidates that can disrupt the spread and progression of the virus. The identification of drug molecules through experimental studies is time-consuming and expensive, so there is a need for developing alternative strategies like in silico approaches which can yield better outcomes in less time. Herein, we selected transmembrane protease serine 2 (TMPRSS2) enzyme, a potential pharmacological target against SARS-CoV-2, involved in the spread and pathogenesis of the virus. Since 3D structure is not available for this protein, the present study aims at homology modelling and validation of TMPRSS2 using Swiss-model server. Validation of the modelled TMPRSS2 using various online tools confirmed model accuracy, topology and stereochemical plausibility. The catalytic triad consisting of Serine-441, Histidine-296 and Aspartic acid-345 was identified as active binding site of TMPRSS2 using existing ligands. Molecular docking studies of various drugs and phytochemicals against the modelled TMPRSS2 were performed using camostat as a standard drug. The results revealed eight potential drug candidates, namely nafamostat, meloxicam, ganodermanontriol, columbin, myricetin, proanthocyanidin A2, jatrorrhizine and baicalein, which were further studied for ADME/T properties. In conclusion, the study unravelled eight high affinity binding compounds, which may serve as potent antagonists against TMPRSS2 to impact COVID-19 drug therapy.

Nano-ellagic acid: inhibitory actions on aldose reductase and α-glucosidase in secondary complications of diabetes, strengthened by in silico docking studies.

Increased blood sugar levels in prolonged diabetes lead to secondary complications such as retinopathy, neuropathy, and nephropathy, which gradually end in death. Synthesis of nano-phytomedicines from active phytoconstituents for novel emerging applications in the field of pharmaceuticals is of huge interest among researchers. In the present investigation, encapsulated ellagic acid (NEA) was synthesized at four different concentrations (0.2%, 0.3%, 0.4%, 0.5%) using ZnO nanoparticles as encapsulating agent. The surface morphology (fiber-like structures) of the nanoparticles were determined by scanning electron microscopy (SEM) and particle size (161-297 nm) and zeta potential (- 54.9-38.4 mV) were determined by dynamic light scattering technique. Further, the α-glucosidase and aldose reductase enzymes were significantly inhibited by the 0.4% of NEA compared to the other concentrations which strengthened our studies in overcoming the secondary complications of diabetes. The interaction analysis between ellagic acid and insulin receptor found Hit 1 among 10 executed ∆G score and energy of - 5.76, - 4.63 kcal/mol and formed polar bond with Arg 113 with - 1.175 Å distance. The residues Arg115, Lys116, Phe118, Ile115, Arg1131, Arg1155, Ile1157, Lys1165 and Phe1186 were found in ligand-protein interactions. ADME/T analysis of hit 1 was within the acceptable range without any toxic functional groups, providing a framework for developing novel therapeutics.