New iridoids and phenolic glycosides from nuxia congesta R.Br. ex Fresen with potential inhibitors of SARS-CoV-2 main protease and spike RBD: an in silico approach

The aerial parts of Nuxia congesta R.Br. ex Fresen were chromatographically purified, yielding five new compounds: two iridoids (1,2), one phenylpropanoid glycoside (3), and two rhamnosyl esters (4,5). The compounds were characterised via NMR and HRESIMS. The isolated compounds inhibitory action towards the COVID-19 major protease (M^pro) and receptor-binding domain (RBD) enzymes was evaluated. Comparative molecular docking and binding free energy analyses were conducted based on the binding affinities of the ligand binding domains of the therapeutic targets Mpro and RBD. The results indicated that all compounds effectively interacted with the binding sites of M^pro and RBD receptors, exhibiting a greater affinity for the M^pro receptor. The binding energy to M^pro ranged between −7.8 and −8.1 kcal/mol, however for RBD receptors it ranged from −7.0 to −7.3 kcal/mol. This research supports the efficacy of isolated compounds as antiviral medications, especially in the context of COVID-19.