Abstract
High infection caused by mutations of SARS-CoV-2 calls for new prevention strategy. Ganoderma lucidum known as a superior immunoenhancer exhibits various antiviral effects, whether it can resist SARS-CoV-2 remains unclear. Herein, virtual screening combined with in vitro hACE2 inhibition assays were used to investigate its anti SARS-CoV-2 effect. Potential 54 active components, 80 core targets and 20 crucial pathways were identified by the component-target-pathway network. The binding characters of these components to hACE2 and its complexes with spike protein including omicron variant was analyzed by molecular docking. Lucidenic acid A was selected as the top molecule with high affinity to all receptors by forming hydrogen bonds. Molecular dynamics simulation showed it had good binding stability with the receptor proteins. Finally, in vitro FRET test demonstrated it inhibited the hACE2 activity with IC50 2 μmol/mL. Therefore, lucidenic acid A can prevent the virus invasion by blocking hACE2 binding with SARS-CoV-2.
Keywords: Anti-SARS-CoV-2; FRET test; Ganoderma lucidum triterpenoids; Lucidenic acid A (PubChem CID: 14109375); Natural products; Omicron variant.
【저자키워드】 natural products, anti-SARS-CoV-2, omicron variant., Lucidenic acid A (PubChem CID: 14109375), Ganoderma lucidum triterpenoids, FRET test, 【초록키워드】 SARS-CoV-2, Mutation, variant, Infection, molecular docking, antiviral effects, Virtual screening, molecular dynamics, in vitro, omicron, virus, IC50, Spike protein, hACE2, stability, pathway, Omicron variant, target, receptor, binding, Invasion, natural, components, PubChem, high affinity, receptor proteins, hydrogen bonds, component, Prevent, inhibition assay, analyzed, caused, inhibited, were used, demonstrated, complexes, exhibit, Potential, was selected, 【제목키워드】 SARS-CoV-2, Spike protein, binding, Invasion, hACE2 receptor, Prevent, inhibit,