Lancemaside A from Codonopsis lanceolata: Studies on Antiviral Activity and Mechanism of Action against SARS-CoV-2 and Its Variants of Concern

Several plant-derived natural products with anti-SARS-CoV-2 activity have been evaluated for the potential to serve as chemotherapeutic agents for the treatment of COVID-19. Codonopsis lanceolata (CL) has long been used as a medicinal herb in East Asian countries to treat inflammatory diseases of th...

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Bibliographic Details
Published in:Antimicrobial agents and chemotherapy 2022-12, Vol.66 (12), p.e0120122-e0120122
Main Authors: Kim, Tai Young, Jeon, Sangeun, Ko, Meehyun, Du, Young Eun, Son, So-Ri, Jang, Dae Sik, Kim, Seungtaek, Lee, C Justin
Format: Article
Language:English
Subjects:
Animals
Antimicrobial Chemotherapy
Antiviral Agents
Antiviral Agents - pharmacology
Chlorocebus aethiops
Codonopsis - metabolism
COVID-19
Humans
SARS-CoV-2
Spike Glycoprotein, Coronavirus
Vero Cells
Virus Internalization
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Summary:Several plant-derived natural products with anti-SARS-CoV-2 activity have been evaluated for the potential to serve as chemotherapeutic agents for the treatment of COVID-19. Codonopsis lanceolata (CL) has long been used as a medicinal herb in East Asian countries to treat inflammatory diseases of the respiratory system but its antiviral activity has not been investigated so far. Here, we showed that CL extract and its active compound lancemaside A (LA) displayed potent inhibitory activity against SARS-CoV-2 infection using a pseudotyped SARS-CoV-2 entry assay system. We demonstrated that this inhibitory effect of LA was due to the alteration of membrane cholesterol and blockade of the membrane fusion between SARS-CoV-2 and host cells by filipin staining and cell-based membrane fusion assays. Our findings also showed that LA, as a membrane fusion blocker, could impede the endosomal entry pathway of SARS-CoV-2 and its variants of concern (VOCs), including Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2), and Omicron (B.1.1.529), in Vero cells with similar of IC values ranging from 2.23 to 3.37 μM as well as the TMPRSS2-mediated viral entry pathway in A549 cells overexpressing ACE2 and TMPRSS2 with IC value of 3.92 μM. We further demonstrated that LA could prevent the formation of multinucleated syncytia arising from SARS-CoV-2 spike protein-mediated membrane fusion. Altogether, the findings reported here suggested that LA could be a broad-spectrum anti-SARS-CoV-2 therapeutic agent by targeting the fusion of viral envelope with the host cell membrane.
ISSN:0066-4804
1098-6596
DOI:10.1128/aac.01201-22