期刊
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
卷 66, 期 12, 页码 -出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/aac.01201-22
关键词
COVID-19; lancemaside A; Omicron; SARS-CoV-2; membrane fusion; triterpenoid saponin
资金
- Institute for Basic Science (IBS)
- Center for Cognition and Sociality [IBS-R001-D2]
- National Research Foundation of Korea (NRF) - Korean government (MSIT) [NRF-2017M3A9G6068245, NRF-2022M3A9J1081343, NRF-2019R1A2C1083945]
The study found that Codonopsis lanceolate extract and its active compound lancemaside A have potent inhibitory activity against SARS-CoV-2 infection. The inhibitory effect is achieved by altering membrane cholesterol and blocking membrane fusion between the virus and host cells. Furthermore, lancemaside A can also block the entry pathways of different SARS-CoV-2 variants and prevent the formation of multinucleated syncytia caused by viral spike protein-mediated membrane fusion.
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 lanceolate (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.1.6172), and Omicron (B.1.1529), in Vero cells with similar of IC50 values ranging from 2.23 to 3.37 mu M as well as the TMPRSS2-mediated viral entry pathway in A549 cells overexpressing ACE2 and TMPRSS2 with IC50 value of 3.92 mu M. 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.
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