By modifying immunological response and protease activity, fungus bioactive substances such as polysaccharides, terpenes, and cordycepin have demonstrated antiviral efficacy against coronavirus.
The Polyporaceae family includes the common Chinese medicinal fungus known as Ganoderma lucidum. This fungus’ bioactive components have been extracted, and they exhibit strong immune-stimulating and antiviral properties.
By blocking the connection between the viral spike protein and the host cell receptor angiotensin-converting enzyme 2, researchers have examined whether Ganoderma lucidum can stop SARS-CoV-2 host cell entry (ACE2).
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Antiviral Properties of Ganoderma lucidum
The initial screening of Ganoderma lucidum resulted in the discovery of 574 antiviral target proteins and 54 bioactive chemicals. With the help of these targets and SARS-CoV-2-specific targets, 80 anti-SARS-CoV-2 targets from Ganoderma lucidum were found.
The targets associated with inflammation, infection, cancer, and other pathways were integrated into a network model of Ganoderma lucidum’s putative antiviral target genes. Scientists proposed that the bioactive chemicals might be employed to treat SARS-CoV-2 infection based on the actions of the identified targets.
Each antiviral compound of Ganoderma lucidum can act on many targets, according to the analysis of the target-compound network. More specifically, it was discovered that 54 identified chemicals interacted with 80 SARS-CoV-2-related targets. Furthermore, associations between these targets and 20 distinct signalling pathways were discovered. The bulk of these pathways was antiviral and anti-inflammatory.
Dynamics of bioactive compound interactions
By docking each discovered compound independently with the human ACE2, wildtype spike-human ACE2 complex, and omicron spike-human ACE2 complex, the interaction pattern of each drug was identified. This resulted in the discovery of lucidenic acid A, which showed a high affinity for binding to all target receptors.
It was discovered that lucidenic acid A formed a hydrogen bond with human ACE2 when it interacted with it, preventing the viral spike protein from interacting with ACE2. Overall, these findings suggest that lucidenic acid A can effectively prevent wild-type SARS-CoV-2 and its variations from entering host cells.
Activity of lucidenic acid A against viruses
The spike-ACE2 complex is made unstable by lucidenic acid A, according to the results of a molecular dynamics simulation. This emphasizes even further how effective lucidenic acid A is at preventing spike-ACE2 interaction.
Further investigation revealed that even at low micromolar concentrations, lucidenic acid A inhibits the binding activity of ACE2. This may be how lucidenic acid A primarily works to stop SARS-CoV-2 from infecting host cells.
Antiviral Medicine Against SARS-CoV-2
The study conducts a thorough screening of bioactive chemicals produced from Ganoderma lucidum to find potential antiviral medicines against SARS-CoV-2. Triterpenes and sterols, which are mostly found in discovered substances, have antiviral and anti-inflammatory properties.
Molecular docking tests reveal lucidenic acid A to be a strong anti-SARS-CoV-2 substance with a high affinity for the human ACE2 receptor. At low micromolar concentrations, lucidenic acid A reduces the binding activity of ACE2 in a mechanistic manner. Consequently, this prevents the interaction between human ACE2 and SARS-CoV-2 spike.
Notably, lucidenic acid A blocks the entry of omicron and wild-type SARS-CoV-2 into host cells.
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