Comprehensive In Silico Screening of the Antiviral Potentialities of a New Humulene Glucoside from Asteriscus hierochunticus against SARS-CoV-2

Vincent O Imieje,Abiodun Falodun,Eslam B Elkaeed,Ahmad E Mostafa,Ahmed A Zaki,Ahmed M Metwaly,Wagdy Eldehna

doi:10.1155/2021/5541876

Abstract

Chromatographic fractionation of the methanolic extract of Asteriscus hierochunticus whole plant led to the identification of a new humulene glucoside (1). The chemical structure of the isolated compound was elucidated by IR, 1D, 2D NMR, and HRESIMS data analysis to be (-)-(2Z,6E,9E)8α-hydroxy-2,6,9-humulatrien-1(12)-olide. In this study, we report the in silico binding affinities of 1 against four different SARS-CoV-2 proteins (COVID-19 main protease (PDB ID: 6lu7), nonstructural protein (PDB ID: 6W4H), RNA-dependent RNA polymerase (PDB ID: 7BV2), and SARS-CoV-2 helicase (PDB ID: 5RMM)). The isolated compound showed excellent binding affinity values (ΔG) of −21.65, −20.05, −28.93, and −21.73 kcal/mol, respectively, against the target proteins compared to the cocrystallized ligands that exhibited ΔG values of −23.75, −17.65, −23.57, and −15.30 kcal/mol, respectively. Further in silico investigations of the isolated compound (1) for its ADMET and toxicity profiles revealed excellent drug likeliness. On the other hand, the results obtained from in vitro antitrypanosomal, antileishmanial, and antimalarial activities of (1) were not promising.

Highlights

Chromatographic fractionation of the methanolic extract of Asteriscus hierochunticus whole plant led to the identification of a new humulene glucoside (1). e chemical structure of the isolated compound was elucidated by IR, 1D, 2D NMR, and HRESIMS data analysis to be (-)-(2Z,6E,9E)8α-hydroxy-2,6,9-humulatrien-1(12)-olide
We report the in silico binding affinities of 1 against four different SARS-CoV-2 proteins (COVID-19 main protease (PDB ID: 6lu7), nonstructural protein (PDB ID: 6W4H), RNA-dependent RNA polymerase (PDB ID: 7BV2), and SARS-CoV-2 helicase (PDB ID: 5RMM)). e isolated compound showed excellent binding affinity values (ΔG) of −21.65, −20.05, −28.93, and −21.73 kcal/mol, respectively, against the target proteins compared to the cocrystallized ligands that exhibited ΔG values of −23.75, −17.65, −23.57, and −15.30 kcal/mol, respectively
Wiklund is a widely distributed shrub that belongs to family Asteraceae and found in tropical regions, including Asia, the Americas, Africa, the Middle East and the Mediterranean region, Europe, and some islands in the Pacific and Atlantic oceans [24]. e genus Asteriscus is used in folk medicine for treatment and managing of different disease conditions, such as inflammations, fevers, cancers, stomach aches, bronchitis, hemorrhoids, and other disorders [25]