Spontaneous binding of potential COVID-19 drugs (Camostat and Nafamostat) to human serine protease TMPRSS2

Identification of novel TMPRSS2 inhibitors for COVID-19 using e-pharmacophore modelling, molecular docking, molecular dynamics and quantum mechanics studies

“…Since TMPRSS2 mRNA is abundant in a variety of tissues including the prostate, kidney, small intestine, lung, and stomach and others, it is linked to the progression and severity of the illness [ 1 , 18 , 27 , 28 ].As a result, TMPRSS2 processing is amongst the most important stages in activating the SARS-CoV-2 S protein's membrane activity [ 29 ]. Because of the extreme role of TMPRSS2, it might be a promising therapeutic target in the struggle against COVID-19 infection [ 30 , 31 ].…”

Discovery of diminazene as a dual inhibitor of SARS-CoV-2 human host proteases TMPRSS2 and furin using cell-based assays

“…In order to explain the ability of diminazene to inhibit TMPRSS2 and furin and to compare its binding with that of camostat and nafamostat to these targets, molecular docking studies were performed using several docking programs. Molecular docking of diminazene by using Autodock Vina 55 revealed that it can bind to TMPRSS2 catalytic binding site consisting of the triad residues HIS296, ASP345, and SER441 ( Figure 8 , Supplementary Table S8-1 ) similar to camostat and nafamostat, 56 suggesting they may share the same inhibitory mechanism. Diminazene can also bind to the furin catalytic/binding site consisting of the residues ASN192, LEU227, SER253, ASP258, ASP306, THR367, and SER368 ( Figure 9 ).…”

Molecular dynamics simulations reveal the importance of conformational changes, glycosylation, mutations, and drug repurposing for the Sars-Cov-2 spike protein

“…The same goes for nafamostat, which we suggested as a putative RBD binder, [19] but it is proposed to act as a transmembrane serine protease 2 (TMPRSS2) inhibitor in the lownanomolar range. [68,69] Table 1. Summary of the drugs, recently identified as protective against SARS-CoV-2 in vitro, proposed as RBD binders by MD simulations.…”