QSAR and molecular docking studies of isatin and indole derivatives as SARS 3CL(pro) inhibitors

The 3C-like protease (3CL(pro)), known as the main protease of SARS-COV, plays a vital role in the viral replication cycle and is a critical target for the development of SARS inhibitor. Comparative sequence analysis has shown that the 3CL(pro) of two coronaviruses, SARS-CoV-2 and SARS-CoV, show high structural similarity, and several common features are shared among the substrates of 3CL(pro) in different coronaviruses. The goal of this study is the development of validated QSAR models by CORAL software and Monte Carlo optimization to predict the inhibitory activity of 81 isatin and indole-based compounds against SARS CoV 3CL(pro). The models were built using a newer objective function optimization of this software, known as the index of ideality correlation (IIC), which provides favorable results. The entire set of molecules was randomly divided into four sets including: active training, passive training, calibration and validation sets. The optimal descriptors were selected from the hybrid model by combining SMILES and hydrogen suppressed graph (HSG) based on the objective function. According to the model interpretation results, eight synthesized compounds were extracted and introduced from the ChEMBL database as good SARS CoV 3CL(pro) inhibitor. Also, the activity of the introduced molecules further was supported by docking studies using 3CL(pro) of both SARS-COV-1 and SARS-COV-2. Based on the results of ADMET and OPE study, compounds CHEMBL4458417 and CHEMBL4565907 both containing an indole scaffold with the positive values of drug-likeness and the highest drug-score can be introduced as selected leads. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13065-023-00947-w.