Lucidenic acid A inhibits the binding of hACE2 receptor with spike protein to prevent SARS-CoV-2 invasion.

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.

Ganoderma lucidum: A potential source to surmount viral infections through ß-glucans immunomodulatory and triterpenoids antiviral properties.

Ganoderma lucidum (G. lucidum) polysaccharides and triterpenoids are the major bioactive compounds and have been used as traditional medicine for ancient times. Massive demands of G. lucidum have fascinated the researchers towards its application as functional food, nutraceutical and modern medicine owing to wide range of application in various diseases include immunomodulators, anticancer, antiviral, antioxidant, cardioprotective, hepatoprotective. G. lucidum polysaccharides exhibit immunomodulatory properties through boosting the action of antigen-presenting cells, mononuclear phagocyte system, along with humoral and cellular immunity. ß-Glucans isolated from G. lucidum are anticipated to produce an immune response through pathogen associated molecular patterns (PAMPs). ß-Glucans after binding with dectin-1 receptor present on different cells include macrophages, monocytes, dendritic cells and neutrophils produce signal transduction that lead to trigger the mitogen-activated protein kinases (MAPKs), T cells and Nuclear factor-κB (NF-κB) that refer to cytokines production and contributing to immune response. While triterpenoids produce antiviral effects through inhibiting various enzymes like neuraminidase, HIV-protease, DENV2 NS2B-NS3 protease and HSV multiplication. Polysaccharides and triterpenoids adjunct to other drugs exhibit potential action in prevention and treatment of various diseases. Immunomodulators and antiviral properties of this mushroom could be a potential source to overcome this current pandemic outbreak.