CANDIDATURE OF THE SYNTHETIC CASPASE INHIBITORS AS NEW ANTI-SARS-COV-2 DRUG DISCOVERY, IN-SILICO MOLECULAR DOCKING

The new pandemic virus identified as severe acute respiratory syndrome Coronavirus 2 is the etiological agent responsible for the pneumonia outbreak that ended with respiratory failure. The main protease (M^PRO) is a key enzyme for SARS-CoV-2, which plays a pivotal role in mediating viral replication and transcription, making it an attractive drug target for this virus. Here, we determine the mechanism-based for binding and interactions between the reported caspase inhibitors and M^PRO, by computer-aided drug design molecular docking. In addition to the prediction of physicochemical properties, pharmacokinetics, and drug-likeness profile in-silico as well as reviewing the previously reported antiviral activity of the caspase inhibitors and how could the viruses get an advantage from the apoptosis process. Molecular operating environment is used for docking between thirteen reported caspase inhibitors compounds and SARS-COV-2 main protease using HWH (~ {N}- [2- (5- fluoranyl-1~ {H}-indol-3-yl) ethyl] ethanamide) as a reference. The results have shown that almost all of the reported anti-caspase compounds revealed acceptable binding with good docking scores and favorable in-silico pharmacokinetic profile that might promise a rapid discovery of drug leads with clinical potential in response to new infectious diseases for which no specific drugs or vaccines are available.