leupeptins has been researched along with camostat* in 3 studies
3 other study(ies) available for leupeptins and camostat
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Strong Binding of Leupeptin with TMPRSS2 Protease May Be an Alternative to Camostat and Nafamostat for SARS-CoV-2 Repurposed Drug: Evaluation from Molecular Docking and Molecular Dynamics Simulations.
The unprecedented coronavirus SARS-CoV-2 outbreak at Wuhan, China, caused acute respiratory infection to humans. There is no precise vaccine/therapeutic agents available to combat the COVID-19 disease. Some repurposed drugs are saving the life of diseased, but the complete cure is relatively less. Several drug targets have been reported to inhibit the SARS-CoV-2 virus infection, in that TMPRSS2 (transmembrane protease serine 2) is one of the potential targets; inhibiting this protease stops the virus entry into the host human cell. Camostat mesylate, nafamostat, and leupeptin are the drugs, in which the first two drugs are being used for COVID-19 and leupeptin also tested. To consider these drugs as the repurposed drug for COVID-19, it is essential to understand their binding affinity and stability with TMPRSS2. In the present study, we performed the molecular docking and molecular dynamics (MD) simulation of these molecules with the TMPRSS2. The docking study reveals that leupeptin molecule strongly binds with TMPRSS2 protein than the other two drug molecules. The RMSD and RMSF values of MD simulation confirm that leupeptin and the amino acids of TMPRSS2 are very stable than the other two molecules. Furthermore, leupeptin forms interactions with the key amino acids of TMPRSS2 and the same have been maintained during the MD simulations. This structural and dynamical information is useful to evaluate these drugs to be used as repurposed drugs, however, the strong binding profile of leupeptin with TMPRSS2, suggests, it may be considered as a repurposed drug for COVID-19 disease after clinical trial. Topics: Antiviral Agents; Benzamidines; COVID-19; COVID-19 Drug Treatment; Drug Repositioning; Esters; Guanidines; Humans; Leupeptins; Molecular Docking Simulation; Molecular Dynamics Simulation; Protein Binding; SARS-CoV-2; Serine Endopeptidases | 2021 |
Arginine vasopressin transport and metabolism in the pigmented rabbit conjunctiva.
The purpose of this study was to evaluate the transepithelial transport and metabolism of arginine vasopressin (AVP) in the pigmented rabbit conjunctiva, both in the absence and presence of protease inhibitors. The apparent permeability coefficient, P(app), for 3H-AVP was determined in the modified Ussing chamber, and AVP metabolites were monitored by reversed phase HPLC using a C18 column. At 50 nM donor 3H-AVP, the P(app) in the mucosal-to-serosal (ms) direction was about five times higher than that in the opposite direction. Excess (0.1 mM) AVP decreased the P(app) for labelled AVP in the mucosal-to-serosal (ms) direction by about 50%. However, intact AVP transport showed neither concentration nor direction dependence. HPLC analysis revealed two subspecies of 3H-AVP in the receiver fluid and virtually no degradation products in the donor fluid following 3 h flux experiments. 3H-AVP transported in the ms direction underwent extensive hydrolysis (73%), which was decreased by 33% with mucosal application of 2 mM camostat mesylate (an aminopeptidase inhibitor) or by 27% with 0.5 mM leupeptin (a serine protease inhibitor). By contrast, 3H-AVP transported in the serosal-to-mucosal (sm) direction resulted in only 37% hydrolysis, and mucosal application of either inhibitor did not significantly affect the P(app) for intact AVP. These data suggest that intact AVP transport in the conjunctiva may be mediated mostly by passive diffusion and enzymatic degradation of AVP may be mediated by proteolytic enzymes present on the mucosal side of the conjunctiva. Topics: Animals; Arginine Vasopressin; Biological Transport; Chromatography, High Pressure Liquid; Conjunctiva; Esters; Gabexate; Guanidines; In Vitro Techniques; Leupeptins; Male; Protease Inhibitors; Rabbits; Tritium | 1998 |
Cathepsin B in the growth of colorectal cancer: suppressive effect of leupeptin on the growth of DMH-induced rat colon neoplasm.
Cathepsin B, a thiol protease, has been reported to be involved in cancer progression and metastasis. The suppressive effects of two kinds of protease inhibitors, leupeptin and dietary camostate (FOY-305), on tumorigenesis and progression in 1, 2-dimethylhydrazine (DMH)-induced rat colon neoplasm were examined in relation to tissue cathepsin B activity. Male Donryu rats were treated with leupeptin or FOY-305 during or after the administration of DMH. There were no significant differences in average tumor numbers among all DMH-treated groups. However, the percentage of small tumors was significantly higher in the group in which leupeptin was supplied during DMH administration. This trend was not recognized in the FOY-305-treated groups. The ratio of cathepsin B activity in the tumors to that in the tumor-bearing tissue (T/Tb) was significantly increased with increasing tumor size (P = 0.009). The cathepsin B activity levels in the tumor-bearing mucosa in the groups which received leupeptin or FOY-305 following DMH treatment were both significantly lower than that in the group which received neither protease inhibitor (P = 0.046 and P = 0.0067, respectively). The results obtained indicate that leupeptin may have suppressed tumor growth by lowering the tissue cathepsin B activity. Topics: 1,2-Dimethylhydrazine; Animals; Carcinogens; Cathepsin B; Colonic Neoplasms; Dimethylhydrazines; Esters; Gabexate; Guanidines; Leupeptins; Male; Protease Inhibitors; Rats | 1996 |