Computational modeling predicts potential effects of the herbal infusion “horchata” against COVID-19

Tejera, Eduardo; Pérez-Castillo, Yunierkis; Toscano, Gisselle; Noboa, Ana Lucía; Ochoa-Herrera, Valeria; Giampieri, Francesca; Álvarez-Suarez, José M.

Bioactive plant-derived molecules have emerged as therapeutic alternatives in the fight against the COVID-19 pandemic. In this investigation, principal bioactive compounds of the herbal infusion “horchata” from Ecuador were studied as potential novel inhibitors of the SARS-CoV-2 virus. The chemical composition of horchata was determined through a HPLC-DAD/ESI-MS(n) and GC–MS analysis while the inhibitory potential of the compounds on SARS-CoV-2 was determined by a computational prediction using various strategies, such as molecular docking and molecular dynamics simulations. Up to 51 different compounds were identified. The computational analysis of predicted targets reveals the compounds’ possible anti-inflammatory (no steroidal) and antioxidant effects. Three compounds were identified as candidates for M(pro) inhibition: benzoic acid, 2-(ethylthio)-ethyl ester, l-Leucine-N-isobutoxycarbonyl-N-methyl-heptyl and isorhamnetin and for PL(pro): isorhamnetin-3-O-(6-Orhamnosyl-galactoside), dihydroxy-methoxyflavanone and dihydroxyphenyl)-5-hydroxy-4-oxochromen-7-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid. Our results suggest the potential of Ecuadorian horchata infusion as a starting scaffold for the development of new inhibitors of the SARS-CoV-2 M(pro) and PL(pro) enzymes.