Virtual screening plant-derived compounds against SARS-CoV-2 viral proteins using computational tolos

ZÍGOLO, MARÍA ANTONELA; GOYTIA, MATÍAS RIVERO; POMA, HUGO RAMIRO; RAJAL, VERONICA BEATRIZ; IRAZUSTA, VERÓNICA PATRICIA

Congreso; Congreso Conjunto de la Sociedad Argentina de Investigación Bioquímica (SAIB) y la Asociación Civil de Microbiología General (SAMIGE); 2020

The new SARS-CoV-2, responsible for the COVID-19 pandemic, has been threatening public health worldwide for half a year. Plants are great producers of secondary metabolites and as such, especially those from poorly studied regions, they captured the interest of many researchers trying to develop new medicines. Antiviral bioactivities have been described in numerous medicinal plants and associated with compounds like flavonoids, heterosides, terpenes, and triterpenes, organic acids, alkaloids, saponins, and quaternary ammonium salts, among others. The aim of this work was to evaluate compounds of natural origin, mainly from medicinal plants, as potential SARS-CoV-2 inhibitors through docking studies. Molecular docking was performed using AutoDock, with the Lamarckian Genetic Algorithm, to analyse the probability of docking. The viral spike (S) glycoprotein and the main protease Mpro, involved in the recognition of virus by host cells and in viral replication, respectively, were the main molecular targets in this study. These proteins are essential to the transmission and virulence of the virus. By inhibiting anyone of these proteins or both, for a higher active therapy, the severity of the infection will be reduced. Our efforts have been placed in competitively inhibiting the binding of its natural substrates.The best energy binding values for S protein were, in kcal/mol: -19.22 for glycyrrhizin, -17.84 for gitoxin, -12.05 for dicumarol, -10.75 for diosgenin, and -8.12 for delphinidin. For Mpro were, in kcal/mol: -9.36 for spirostan, -8.75 for N-(3-acetylglycyrrhetinoyl)-2-amino-propanol, -8.41 for α-amyrin, -8.35 for oleanane, -8.11 for taraxasterol, and -8.03 for glycyrrhetinic acid. In addition, the synthetic drugs umifenovir, chloroquine, and hydroxychloroquine were used as controls for S protein, while atazanavir and nelfinavir were used for Mpro. Key hydrogen bonds and hydrophobic interactions between natural compounds and the respective viral proteins were identified, allowing us to explain the great affinity obtained in those compounds with the lowest binding energies. These results suggest that these natural compounds could potentially be useful as drugs to be experimentally evaluated against COVID-19. Furthermore, the present study provides molecular details that allow us to propose structural modifications of some compounds to make the interaction between them and viral proteins even more effective.