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

被引:18
作者
Kobayashi, Chisa [1 ,2 ]
Watanabe, Yoshihiro [3 ,4 ]
Oshima, Mizuki [1 ,2 ]
Hirose, Tomoyasu [3 ,4 ]
Yamasaki, Masako [1 ,2 ]
Iwamoto, Masashi [1 ]
Iwatsuki, Masato [3 ,4 ]
Asami, Yukihiro [3 ,4 ]
Kuramochi, Kouji [2 ]
Wakae, Kousho [1 ]
Aizaki, Hideki [1 ]
Muramatsu, Masamichi [1 ]
Sureau, Camille [5 ]
Sunazuka, Toshiaki [3 ,4 ]
Watashi, Koichi [1 ,2 ,6 ,7 ]
机构
[1] Natl Inst Infect Dis, Dept Virol 2, Tokyo 1628640, Japan
[2] Tokyo Univ Sci, Dept Appl Biol Sci, Noda, Chiba 2788510, Japan
[3] Kitasato Univ, Grad Sch Infect Control Sci, Tokyo 1088641, Japan
[4] Kitasato Univ, Omura Satoshi Mem Inst, Tokyo 1088641, Japan
[5] Inst Natl Transfus Sanguine, Lab Virol Mol, F-75739 Paris, France
[6] Natl Inst Infect Dis, Res Ctr Drug & Vaccine Dev, Tokyo 1628640, Japan
[7] JST, MIRAI, Saitama 3320012, Japan
来源
VIRUSES-BASEL | 2022年 / 14卷 / 04期
基金
日本学术振兴会;
关键词
HBV; entry; NTCP; exophillic acid; HDV; inhibitor; antiviral; MEMBRANE TRANSPORTER; ENVELOPE PROTEIN; ANALOGS; CELLS; DNA;
D O I
10.3390/v14040764
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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 mu M and a 50% cytotoxic concentration (CC50) of >30 mu M 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.
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页数:14
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