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

Abstract

A new epoxy ergostane sterol, named versisterol, was isolated from Aspergillus versicolor, an endophytic fungus from Avicennia marina. 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^pro) with an IC₅₀ value of 2.168 ± 0.09 μM. Binding affinities and molecular interactions of versisterol towards 3CL^pro were scrutinized and compared to lopinavir with the help of the combination of docking computations and molecular dynamics (MD) simulation. In silico calculations demonstrated a comparable binding affinity of versisterol with a docking score of −9.4 kcal mol⁻¹, and MM-GBSA binding energy over 200 ns MD simulation of −29.1 kcal mol⁻¹, with respect to lopinavir (−9.8 and −32.2 kcal mol⁻¹, respectively). These findings suggested that versisterol can be an auspicious prototype for developing new 3CL^pro drug candidates against COVID-19.