Versisterol, a new endophytic steroid with 3CL protease inhibitory activity from (Forssk.) Vierh.

A new epoxy ergostane sterol, named versisterol, was isolated from , an endophytic fungus from . The structure of the isolated compound was deduced by means of one- and two-dimensional NMR and high-resolution mass spectrometry. The absolute stereochemistry was elucidated by NOESY analysis, and experimental and calculated time-dependent density functional theory (TD-DFT) circular dichroism spectroscopy. Versisterol inhibited 3CL protease (3CL) with an IC value of 2.168 ± 0.09 μM. Binding affinities and molecular interactions of versisterol towards 3CL were scrutinized and compared to lopinavir with the help of the combination of docking computations and molecular dynamics (MD) simulation. calculations demonstrated a comparable binding affinity of versisterol with a docking score of -9.4 kcal mol, and MM-GBSA binding energy over 200 ns MD simulation of -29.1 kcal mol, with respect to lopinavir (-9.8 and -32.2 kcal mol, respectively). These findings suggested that versisterol can be an auspicious prototype for developing new 3CL drug candidates against COVID-19.