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

Marwa Elsbaey; Mahmoud A A Ibrahim; Mohamed-Elamir F Hegazy

doi:10.1039/d2ra00877g

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

RSC Adv. 2022 Apr 26;12(20):12583-12589. doi: 10.1039/d2ra00877g. eCollection 2022 Apr 22.

Authors

Marwa Elsbaey¹, Mahmoud A A Ibrahim², Mohamed-Elamir F Hegazy³

Affiliations

¹ Pharmacognosy Department, Faculty of Pharmacy, Mansoura University Mansoura 35516 Egypt marwaelsebay1611@mans.edu.eg.
² Computational Chemistry Laboratory, Chemistry Department, Faculty of Science, Minia University Minia 61519 Egypt.
³ Chemistry of Medicinal Plants Department, National Research Centre Giza 12622 Egypt.

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.