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The rapid outbreak of SARS-Coronavirus 2 (SARS-CoV-2) caused a serious global public health threat. The spike ‘S’ protein of SARS-CoV-2 and ACE2 of the host cell are being targeted to design and discover new drugs to control Covid-19 disease. Similarly, a transmembrane serine protease, TMPRSS2 of the host cell has been found to play a significant role in proteolytic cleavage of viral spike protein priming to the receptor ACE2 present in human cell. However, three dimensional structure and inhibition mechanism of TMPRSS2 is yet to be explored experimentally. Hence, in the present study we have generated a homology model of TMPRSS2 and studied its binding properties with experimentally studied inhibitors <i>viz.</i> Camostat mesylate, Nafamostat and Bromhexine hydrochloride (BHH) using molecular docking technique. Docking analysis revealed that the Camostat mesylate and its structural analogue Nafamostat interacts strongly with residues His296, Ser441 and Asp435 present in catalytic triad of TMPRSS2. However, BHH interacts with Gln438 and other residues present in the active site pocket of TMPRSS2 through hydrophobic contacts effectively. Thus, these results revealed the inhibition mechanism of TMPRSS2 by known inhibitors Camostat mesylate, Nafamostat and Bromhexine hydrochloride in detail at the molecular level. However, Camostat mesylate shows strong binding as compared to other two inhibitors. This structural information could also be useful to design and discover new inhibitors of TMPRSS2, which may be helpful to prevent the entry to SARS-Coronavirus 2 in human cell.

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The pathological hallmark of Alzheimer's disease is the accumulation of Aβ peptides in human brains. These Aβ peptides can be degraded by several enzymes such as hACE, hECE, hIDE and cathepsin B. Out of which cathepsin B also belongs to the papain super family and has been found in human brains, it has a role in Aβ peptide degradation through limited proteolysis. The Aβ concentrations are maintained properly by its production and clearance via receptor-mediated cellular uptake and direct enzymatic degradation. However, the reduced production of Aβ degrading enzymes as well as their Aβ degrading activity in human brains initiate the process of accumulation of Aβ peptides. So it becomes essential to investigate the molecular interactions involved in the process of Aβ degradation in detail at the atomic level. Hence, homology modeling, molecular docking and molecular dynamics simulation techniques have been used to explore the possible role of cathepsin B from Hordeum vulgare in the degradation of amyloid beta (Aβ) peptides. The homology model of cathepsin B from Hordeum vulgare shows good similarity with human cathepsin B. Molecular docking and MD simulation results revealed that the active site residues Cys32, HIS112, HIS113 are involved in the catalytic activity of cathepsin B. The sulfhydryl group of the Cys32 residue of cathepsin B from Hordeum vulgare cleaves the Aβ peptide from the carboxylic end of Glu11. Hence, this structural study might be helpful in designing alternative strategies for the treatment of AD.

Objective To isolate and identify the bioactive component from Cymbopogon martinii having GLUT2 transporter inhibitory activity – towards development of a novel strategy for treatment of diabetes mellitus. Method Isolation of bioactive component was carried out using differential solvent extraction, HPTLC and HPLC, and identification was done by GC-MS. In-vitro studies on intestine, liver, kidney and in-vivo assessment by OGTT and long-term treatment on diabetic rats were carried out. Key findings Geraniol was isolated and identified as bioactive component. Intestinal glucose absorption demonstrated 60.28% inhibition of transport at 648.34 μm of geraniol. It was found to inhibit glucose release from liver on adrenaline challenge by 89.82% at 324.17 μm/ml. Kidney glycogen content doubled using 648.34 μm of geraniol as compared to control. Geraniol demonstrated 2.14 times higher renal glucose output than diabetic control. OGTT demonstrated prevention of postprandial spikes. Prolonged treatment for 60 days with 29.37 mm/kg B.W. twice a day of geraniol improved the lipid profile, HbA1C levels and renal parameters. In mRNA studies for 10 days, over expression of GLUT2 was prevented by geraniol. Conclusions Inhibition of GLUT2 by geraniol has the potential to reduce hyperglycaemia and prevent secondary complications in diabetes.