Benjamin Weiner

When designing drugs to inhibit viral enzymes, such as SARS-CoV-2 exonuclease, the half maximal inhibitory concentration (IC50) is an important parameter of the kinetics of a particular inhibitor that determines the necessary concentration of a given inhibitor to halve the activity of the inhibited enzyme. Through this project, we created a web app that serves as an IC50 calculator for enzyme kinematics data taken from a plate reader. The data for each concentration is fit using a custom sigmoidal fitting function from which the maximum velocity of each concentration’s dataset can be calculated. From there, the enzyme calculator uses the maximum velocity at each concentration to determine the IC50 of the specific compound being screened. The data for each concentration can be hand-fit as the operator is able to adjust the input range to prevent contamination by undesired artifacts in the data, such as those that arise over long periods of time or at the beginning of a given run. Users can also adjust the fitting method, choosing options that offset processing time and complexity. The enzyme kinetics calculator has been used to screen several potential inhibitors of SARS-CoV-2 and Lassa exonucleases while also cross-checking each potential inhibitor’s effects on human TREX exonucleases to ensure compatibility with a human environment. The kinetics calculator generates a variety of visual and numerical information that allows the user to determine the effects a given inhibitor candidate has on the enzyme in question.