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Bioactive compounds derived from Ganoderma lucidum exhibit anti-SARS-CoV-2 activity
Scientists have identified lucidenic acid A, one of the bioactive compounds of Ganoderma lucidum, as a potential inhibitor of host cell entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The study was recently published in the journal Food and Chemical Toxicology. Study: Lucidenic acid A inhibits the binding of the hACE2 receptor to the spike protein to prevent SARS-CoV-2 invasion. Image credit: Sritakoset / Shutterstock Background Traditional Chinese medicinal plants are rich sources of many bioactive compounds that exhibit anti-inflammatory, antiviral, antioxidant and anticancer effects. As for antiviral effectiveness, bioactive compounds isolated from about 30 medicinal plants have been found to inhibit coronavirus infection through various mechanisms. Bioactive…
Bioactive compounds derived from Ganoderma lucidum exhibit anti-SARS-CoV-2 activity
Scientists have identified lucidenic acid A, one of the bioactive compounds of Ganoderma lucidum, as a potential inhibitor of host cell entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The study was recently published in the journal Food and Chemical Toxicology.
background
Traditional Chinese medicinal plants are rich sources of many bioactive compounds that exhibit anti-inflammatory, antiviral, antioxidant and anticancer effects. As for antiviral effectiveness, bioactive compounds isolated from about 30 medicinal plants have been found to inhibit coronavirus infection through various mechanisms.
Bioactive fungal compounds, including polysaccharides, terpenes and cordycepin, have shown antiviral activity against the coronavirus by modulating immune response and protease activity.
Ganoderma lucidum is a common Chinese medicinal mushroom from the Polyporaceae family. Bioactive compounds isolated from this fungus have shown potent immune-boosting and antiviral activities.
In the current study, scientists examined whether Ganoderma lucidum can prevent SARS-CoV-2 from entering host cells by inhibiting the interaction between viral spike protein and host cell receptor angiotensin-converting enzyme 2 (ACE2).
Screening of bioactive compounds from Ganoderma lucidum
The initial screening of Ganoderma lucidum resulted in the identification of 54 bioactive compounds and 574 antiviral target proteins. Comparing these targets with SARS-CoV-2-specific targets, 80 anti-SARS-CoV-2 targets from Ganoderma lucidum were identified.
A network model of potential antiviral target genes of Ganoderma lucidum was constructed, which included the targets related to inflammation, infection, cancer, and other signaling pathways. Based on the activities of identified targets, scientists hypothesized that the bioactive compounds could be used to treat SARS-CoV-2 infections.
Target-compound network analysis revealed that each Ganoderma lucidum antiviral compound can act on multiple targets. Specifically, 54 identified compounds were found to interact with 80 SARS-CoV-2-related targets. Furthermore, these targets were found to be associated with 20 different signaling pathways. Most of these pathways were antiviral and anti-inflammatory pathways.
Dynamics of interactions of bioactive compounds
The interaction pattern of the identified compounds was determined by docking separately to human ACE2, wild-type spike-human ACE2 complex, and omicron spike-human ACE2 complex. This led to the identification of lucidenic acid A, which showed strong binding affinity for all target receptors.
Lucidenic acid A was found to interact with human ACE2 by forming a hydrogen bond, which subsequently prevents the interaction between viral spike protein and ACE2. Overall, these observations suggest that lucidenic acid A can strongly inhibit the entry of wild-type SARS-CoV-2 and its variants into the host cell.
Antiviral activity of lucidenic acid A
The results of molecular dynamics simulation showed that lucidenic acid A makes the spike-ACE2 complex unstable. This further highlights the ability of lucidenic acid A to prevent the spike-ACE2 interaction.
Further analysis showed that lucidenic acid A inhibits the binding activity of ACE2 even at low micromolar concentrations. This may be the primary mode of action of lucidenic acid A to prevent SARS-CoV-2 from entering host cells.
Study Importance
The study conducts a large-scale screening of bioactive compounds from Ganoderma lucidum to identify potential antiviral agents against SARS-CoV-2. Most of the identified compounds are triterpenes and sterols, which exhibit antiviral and anti-inflammatory effects.
Molecular docking experiments identify lucidenic acid A as a potent anti-SARS-CoV-2 compound that has high binding affinity for human ACE2. Mechanistically, lucidenic acid A inhibits the binding activity of ACE2 at low micromolar concentrations. This subsequently blocks the interaction between SARS-CoV-2 spike and human ACE2.
In particular, lucidenic acid A prevents the entry of wild-type SARS-CoV-2 and its variants, especially Omicron, into the host cell.
Reference:
- Xu J. 2022. Lucidensäure A hemmt die Bindung des hACE2-Rezeptors an das Spike-Protein, um die Invasion von SARS-CoV-2 zu verhindern. Lebensmittel- und chemische Toxikologie. https://www.sciencedirect.com/science/article/abs/pii/S0278691522006366