Integrated screening for beta-lactamases and COVID-19 inhibitors identification of Pharmaceutical Hits and Lead Optimization

Session II, Virtual Room 2: Compounds, Graphs & Climate Change

Beta-lactamase is an enzyme that is involved in drug resistance. Penicillin like antibiotics constitute 60 % of worldwide antibiotic usage. Bacterial cells use beta lactamase to resist penicillin like antibiotics. Employing computer software programs (two different programs); we have generated a model to produce docking studies data using nine different criteria evaluating the virtual compounds. The virtual compounds that we employ are drug like, similar in chemical moieties to known inhibitors, contain privileged structures and are readily available to purchase to test in vitro. Then using a pivot table from excel the duplicates of the virtual compounds with the binding criteria is revealed. Docking studies reveal how tight the virtual compounds are binding at the active site along with structural (the pose at the active site), kinetic data we are searching for a pharmacological hit. Recently we discovered a compound Ractopamine that shows micro molar activity in vitro. Currently we have shown that a potential cancer drug (LG100268) has low micro molar activity in vitro. Eventually after optimizing our pharmaceutical hits with different virtual compounds, we will use synthetic organic chemistry, molecular modeling, and structure activity relationships to advance the projects into lead and drug space with acceptable pharmacokinetic properties. We also are applying our model/ analytical approach to different targets/enzymes in COVID-19.