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J Microbiol Biotechnol. 2019 Jul 9. doi: 10.4014/jmb.0905.05044. [Epub ahead of print]

Elucidation of the Inhibitory Mechanisms of Nipponoparmelia laevior Lichen Extract against Influenza A (H1N1) Virus through Proteomic Analyses.

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Department of Food Science and Technology and Foodborne Virus Research Center, Chonnam National University, Gwangju, 61186, Republic of Korea.
Department of Food Science and Post-harvest Technology, Tay Nguyen University, Buon Ma Thuot 630000, Daklak, Vietnam.
Biological Disaster Analysis Group, Korea Basic Science Institute, Daejeon, 34133, Republic of Korea.


Lichens contain diverse bioactive secondary metabolites with various chemical and biological properties, which have been widely studied. However, details of the inhibitory mechanisms of their secondary metabolites against influenza A virus (IAV) have not been documented. Here, we investigated the antiviral effect of lichen extracts, obtained from South Korea, against IAV in the MDCK cells. Of the lichens tested, Nipponoparmelia laevior (LC24) exhibited the most potent inhibitory effect against IAV infection. LC24 extract significantly increased cell viability, and reduced apoptosis in IAV-infected cells. The LC24 extract also markedly reduced (~ 3.2 log-fold) IAV mRNA expression after 48 h of infection. To understand the antiviral mechanism of LC24 against IAV, proteomic (UPLC-HDMSE) analysis was performed to compare proteome modulation in IAV-infected (V) vs. mock (M) and LC24+IAV (LCV) vs. V cells. Based on Ingenuity Pathway Analysis (IPA), LC24 inhibited IAV infection by modulating several antiviral-related genes and proteins (HSPA4, HSPA5, HSPA8, ANXA1, ANXA2, HIF-1α, AKT1, MX1, HNRNPH1, HNRNPDL, PDIA3, and VCP) via different signaling pathways, including HIF-1α signaling, unfolded protein response, and interferon signaling. These molecules were identified as the specific biomarkers for controlling IAV in vitro and further confirmation of their potential against IAV in vivo is required. Our findings provide a platform for further studies on the application of lichen extracts against IAV.


2-0-methylrhizonic acid; Nipponoparmelia laevior; anti-influenza A virus; lichens; proteomics

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