SARS-CoV-2 main protease inhibitors from the stem barks of Discoglypremna caloneura (Pax) Prain (Euphorbiaceae) and Pterocarpus erinaceus Poir (Fabaceae) and their molecular docking investigation

Abstract

The main viral protease (Mpro) of SARS-CoV-2 provides an excellent target for antivirals, due to its essential and conserved function in the viral replication cycle. We reported in this study, the SARS-CoV-2 main protease inhibitory effect of twelve compounds isolated from D. caloneura and P. erinaceus together with four derivatives. Among the effectively tested samples, two derivatized compounds displayed significant improvement on the activity from the starting material, friedelin (1) through the acetoreduced (2) to the acetoxy product (3) with respective IC50 values of 42.89, 29.69 and 19.39 µg/mL. The latter displayed the highest activity although lower as compared to that of baicalein, the positive control with IC50 0.41 µg/mL. The molecular docking study showed that an increase in the number of hydrogen bonds between compounds and active site of Mpro resulted in increased inhibition. Graphical Abstract