Abstract
The new SARS-CoV-2, responsible for the COVID-19 pandemic, has been threatening public health worldwide for more than a year. 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. The viral spike (S) glycoprotein and the main protease M pro , involved in the recognition of virus by host cells and in viral replication, respectively, were the main molecular targets in this study. Molecular docking was performed using AutoDock, which allowed us to select the plant actives with the highest affinity towards the viral targets and to identify the interaction molecular sites with the SARS-CoV2 proteins. 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 M pro 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 M pro . 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.
Keywords: 3-Chymotrypsin-like protease; Antiviral activity; Docking; SARS-CoV-2; Spike glycoprotein.
【저자키워드】 SARS-CoV-2, spike glycoprotein, docking, antiviral activity, 3-chymotrypsin-like protease, 【초록키워드】 COVID-19, public health, SARS-CoV2, Chloroquine, Hydroxychloroquine, S protein, spike, COVID-19 pandemic, spike glycoprotein, molecular docking, Viral proteins, Proteins, drug, docking, protease, antiviral activity, virus, glycyrrhizin, Glycyrrhetinic acid, Replication, plants, viral replication, Control, target, nelfinavir, glycoprotein, molecular, umifenovir, inhibitor, binding, AutoDock, Hydrogen bond, Interaction, Atazanavir, Chymotrypsin-like protease, host cells, host cell, hydrogen, Docking studies, Recognition, Viral protein, Compound, M pro, chymotrypsin, hydrophobic, molecular target, viral spike, hydrophobic interactions, highest affinity, new SARS-CoV-2, amyrin, delphinidin, dicumarol, taraxasterol, lowest, responsible, identify, evaluate, involved, addition, evaluated, was performed, were used, in viral, explain, hydrophobic interaction, 【제목키워드】 Protein, Compound, SARS-CoV-2 viral, computational tool,