A Computational Effort to Untangling Anti-SARS-CoV-2 Effects of Oleanolic Acid Analogues

Considering urgent need for novel drugs to target severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we reported at least four Kurdish ethno-medical, antipyretic recipes which can be translated into functional antiviral formulations. This computational work highlights the implications of oleanolic acid and its analogues as a cluster of binder candidates of SARS-CoV-2 main protease (Mpro). Through molecular docking and simulation, we found oleanolic acid (-12.6 Kcal/mol) and its two analogues (OA11; ligand I [-14.2 Kcal/mol]) and (OA31; ligand II [-14.0 Kcal/mol]) bound with Mpro (PDB: 6Y84) more reliably than saquinavir (-8.1 Kcal/mol), as a canonical drug. Salaspermic acid, (3b)-3-{[(2E)-3-phenylprop-2-enoyl]oxy}olean-12-en-28-oic acid, OA37 and OA40 interacted with catalytic dyad and major amino acid residues of Mpro active sites; these toxic compounds may be future anti-protease drug candidates. This study proposes this set of anti-protease pentacyclic triterpenoids should be assayed against SARS-CoV-2 at in vitro level or in clinical settings.