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


Xu J. Yang W. Pan Y. Xu H. He L. Zheng B. Xie Y. Wu X.
November 2022Elsevier Ltd

Food and Chemical Toxicology
2022#169

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.

Anti-SARS-CoV-2 , FRET test , Ganoderma lucidum triterpenoids , Lucidenic acid A (PubChem CID: 14109375) , Natural products , Omicron variant

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State Key Laboratory of Subtropical Silviculture, Zhejiang A&F University, Linan, 311300, China
Zhejiang Provincial Key Laboratory of Characteristic Traditional Chinese Medicine Resources Protection and Innovative Utilization, Zhejiang A&F University, Linan, 311300, China
Hangzhou Xihu District Center for Disease Control and Prevention, Hangzhou, 310030, China
Zhejiang Provincial Academy of Forestry, Zhejiang, Hangzhou, 310000, China
National Innovation Alliance of Lingzhi and Sanyeqing Industry, Linan, 311300, China
Department of Biology, School of Sciences and Humanities, Nazarbayev University, Nur-Sultan, Kazakhstan

State Key Laboratory of Subtropical Silviculture
Zhejiang Provincial Key Laboratory of Characteristic Traditional Chinese Medicine Resources Protection and Innovative Utilization
Hangzhou Xihu District Center for Disease Control and Prevention
Zhejiang Provincial Academy of Forestry
National Innovation Alliance of Lingzhi and Sanyeqing Industry
Department of Biology

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