Evaluating the potency of Sulawesi propolis compounds as ACE-2 inhibitors through molecular docking for COVID-19 drug discovery preliminary study

Abstract

Coronavirus disease (COVID-19) is a global pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Up to date, there has been no specific cure to treat the disease. Indonesia is one of the countries that is still fighting to control virus transmission. Yet, at the same time, Indonesia has a rich biodiversity of natural medicinal products that potentially become an alternative cure. Thus, this study examined the potency of a natural medicinal product, Sulawesi propolis compounds produced by Tetragonula sapiens, inhibiting angiotensin-converting activity enzyme-2 (ACE-2), a receptor of SARS-CoV-2 in the human body. In this study, molecular docking was done to analyze the docking scores as the representation of binding affinity and the interaction profiles of propolis compounds toward ACE-2. The results illustrated that by considering the docking score and the presence of interaction with targeted sites, five compounds, namely glyasperin A, broussoflavonol F, sulabiroins A, (2S)-5,7-dihydroxy-4'-methoxy-8-prenylflavanone and isorhamnetin are potential to inhibit the binding of ACE-2 and SARS-CoV-2, with the docking score of -10.8, -9.9, -9.5, -9.3 and -9.2 kcal/mol respectively. The docking scores are considered to be more favorable compared to MLN-4760 as a potent inhibitor.

Keywords: ACE-2; COVID-19; Molecular docking; Potent inhibitor; Sulawesi propolis.

Fig. 1

Docking score between the test ligands and ACE-2. (+) MLN-4760, (1) sulabiroins A, (2) sulabiroins B, (3) 2′,3′-dihydro-3′-hydroxypapuanic acid, (4) (−)-papuanic acid, (5) (−)-isocalolongic acid, (6) isopapuanic acid, (7) isocalopolyanic acid, (8) glyasperin A, (9) broussoflavonol F, (10) (2S)-5,7-dihydroxy-4′-methoxy-8-prenylflavanone, (11) isorhamnetin, (12) (1′S)-2-trans, 4-trans-abscisic acid, (13) (1′S)-2-cis, 4-trans-abscisic acid.

Fig. 2

Visualization of the molecular interactions of ACE-2 with various ligands. (a) MLN-4760, (b) glyasperin A, (c) broussoflavonol F, (d) sulabiroins A, (e) (2S)-5,7-dihydroxy-4′-methoxy-8-prenylflavanone, (f) isorhamnetin. The purple lines denote the ligand structure, whereas the brown lines denote the structure of amino acid residues. The molecular interactions are reflected as dashed lines and arcs. The green dashed lines between atoms represent hydrogen bonds, and the numbers above these lines indicate the length of the bond. In the meantime, the arcs with spokes radiating toward the ligand atoms represent hydrophobic interactions. The atoms involve in hydrophobic interactions are indicated by the presence of spokes radiating back (Wallace et al., 1995).