VIRTUAL SCREENING OF PLANT-DERIVED COMPOUNDS AGAINST SARS-CoV-2 VIRAL PROTEINS USING COMPUTATIONAL TOOLS

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

Congreso; CONGRESO SAIB-SAMIGE 2020; 2020

: The 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. 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.