Fungal Secondary Metabolite Exophillic Acid Selectively Inhibits the Entry of Hepatitis B and D Viruses

Current anti-hepatitis B virus (HBV) drugs are suppressive but not curative for HBV infection, so there is considerable demand for the development of new anti-HBV agents. In this study, we found that fungus-derived exophillic acid inhibits HBV infection with a 50% maximal inhibitory concentration (I...

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Bibliographic Details
Published in:Viruses 2022-04, Vol.14 (4), p.764
Main Authors: Kobayashi, Chisa, Watanabe, Yoshihiro, Oshima, Mizuki, Hirose, Tomoyasu, Yamasaki, Masako, Iwamoto, Masashi, Iwatsuki, Masato, Asami, Yukihiro, Kuramochi, Kouji, Wakae, Kousho, Aizaki, Hideki, Muramatsu, Masamichi, Sureau, Camille, Sunazuka, Toshiaki, Watashi, Koichi
Format: Article
Language:English
Subjects:
Antibodies
Antigens
Antiviral agents
Benzoates
Cell culture
Chromatography
Cytotoxicity
Drug resistance
entry
exophillic acid
Galactosides
Genomes
HBV
HDV
Hep G2 Cells
Heparan sulfate
Hepatitis B
Hepatitis B virus - physiology
Hepatitis C
Hepatitis delta virus
Hepatitis Delta Virus - physiology
Hepatocytes
Humans
Infections
inhibitor
NTCP
Peptides
Proteins
Virus attachment
Virus Internalization
Viruses
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Summary:Current anti-hepatitis B virus (HBV) drugs are suppressive but not curative for HBV infection, so there is considerable demand for the development of new anti-HBV agents. In this study, we found that fungus-derived exophillic acid inhibits HBV infection with a 50% maximal inhibitory concentration (IC50) of 1.1 µM and a 50% cytotoxic concentration (CC50) of >30 µM in primary human hepatocytes. Exophillic acid inhibited preS1-mediated viral attachment to cells but did not affect intracellular HBV replication. Exophillic acid appears to target the host cells to reduce their susceptibility to viral attachment rather than acting on the viral particles. We found that exophillic acid interacted with the HBV receptor, sodium taurocholate cotransporting polypeptide (NTCP). Exophillic acid impaired the uptake of bile acid, the original function of NTCP. Consistent with our hypothesis that it affects NTCP, exophillic acid inhibited infection with HBV and hepatitis D virus (HDV), but not that of hepatitis C virus. Moreover, exophillic acid showed a pan-genotypic anti-HBV effect. We thus identified the anti-HBV/HDV activity of exophillic acid and revealed its mode of action. Exophillic acid is expected to be a potential new lead compound for the development of antiviral agents.
ISSN:1999-4915
1999-4915
DOI:10.3390/v14040764