A Novel Tricyclic Polyketide, Vanitaracin A, Specifically Inhibits the Entry of Hepatitis B and D Viruses by Targeting Sodium Taurocholate Cotransporting Polypeptide

@article{Kaneko2015ANT,
  title={A Novel Tricyclic Polyketide, Vanitaracin A, Specifically Inhibits the Entry of Hepatitis B and D Viruses by Targeting Sodium Taurocholate Cotransporting Polypeptide},
  author={Manabu Kaneko and Koichi Watashi and Shinji Kamisuki and Hiroki Matsunaga and Masashi Iwamoto and Fumihiro Kawai and Hirofumi Ohashi and Senko Tsukuda and Satomi Shimura and Ryosuke Suzuki and Hideki Aizaki and Masaya Sugiyama and Sam-Yong Park and Takayoshi Ito and Naoko Ohtani and Fumio Sugawara and Yasuhito Tanaka and Masashi Mizokami and Camille Sureau and Takaji Wakita},
  journal={Journal of Virology},
  year={2015},
  volume={89},
  pages={11945 - 11953}
}
ABSTRACT Anti-hepatitis B virus (HBV) drugs are currently limited to nucleos(t)ide analogs (NAs) and interferons. A challenge of drug development is the identification of small molecules that suppress HBV infection from new chemical sources. Here, from a fungus-derived secondary metabolite library, we identify a structurally novel tricyclic polyketide, named vanitaracin A, which specifically inhibits HBV infection. Vanitaracin A inhibited the viral entry process with a submicromolar 50… Expand
A new class of hepatitis B and D virus entry inhibitors, proanthocyanidin and its analogs, that directly act on the viral large surface proteins
TLDR
PAC and its analogs represent a new class of anti‐HBV agents that directly target the preS1 region of the HBV large surface protein. Expand
Chemical array system, a platform to identify novel hepatitis B virus entry inhibitors targeting sodium taurocholate cotransporting polypeptide
TLDR
Results are the first to show that the chemical array technology represents a powerful platform to identify novel viral entry inhibitors, and one of such compound, NPD8716, a coumarin derivative, interacted with NTCP and inhibited HBV infection without causing cytotoxicity. Expand
Troglitazone Impedes the Oligomerization of Sodium Taurocholate Cotransporting Polypeptide and Entry of Hepatitis B Virus Into Hepatocytes
TLDR
This work represents the first report identifying small molecules and peptides that specifically inhibit the internalization of HBV, and proposes a possible role for NTCP oligomerization in viral entry, which will shed a light on a new aspect of the cellular mechanisms regulating HBV infection. Expand
De Novo Macrocyclic Peptide Inhibitors of Hepatitis B Virus Cellular Entry.
TLDR
Small macrocyclic peptide inhibitors of HBV entry that target the cell-surface receptor for HBV, sodium taurocholate cotransporting polypeptide (NTCP) exhibited no inhibition of NTCP-mediated bile acid uptake, making them appealing candidates for therapeutic development. Expand
Selective hepatitis B and D virus entry inhibitors from the group of pentacyclic lupane-type betulin-derived triterpenoids
TLDR
Derivatives of the birch-derived pentacyclic lupane-type triterpenoid betulin revealed clear NTCP inhibitory potency and selectivity for the virus receptor function of N TCP and therefore are promising drug candidates. Expand
Cyclosporin derivatives inhibit hepatitis B virus entry without interfering with NTCP transporter activity
TLDR
It is found that SCY450 and SCY995 did not impair the NTCP-dependent uptake of bile acids, and inhibited multiple HBV genotypes including a clinically relevant nucleoside analog-resistant HBV isolate. Expand
Reduced hepatitis B and D viral entry using clinically applied drugs as novel inhibitors of the bile acid transporter NTCP
TLDR
Five out of 1280 FDA/EMA-approved drugs were identified that inhibit NTCP-mediated bile acid uptake and HBV/HDV infection in vitro, and Rosiglitazone, zafirlukast, TRIAC, sulfasalazine, and chicago sky blue 6B reduced HBV /HDV infected cells in a dose-dependent manner. Expand
A new strategy to identify hepatitis B virus entry inhibitors by AlphaScreen technology targeting the envelope-receptor interaction.
TLDR
This is the first report for application of AlphaScreen technology that monitors a viral envelope-receptor interaction to identify viral entry inhibitors, and rapamycin, an immunosuppressant, strongly inhibited the LHBs-NTCP interaction. Expand
Development of a mass spectrometric screening assay for hepatitis B virus entry inhibitors.
TLDR
This assay method does not require HBV infection or radioactive 3H-TCA and provides a facile way to identify viral entry inhibitors via measuring bile acid transport activity of NTCP. Expand
Concept of Viral Inhibitors via NTCP.
TLDR
In vitro chemical screening by application of high-throughput affinity-based technologies that target NTCP has identified a variety of unique small molecules that interfere with viral entry. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 56 REFERENCES
Cyclosporin A and its analogs inhibit hepatitis B virus entry into cultured hepatocytes through targeting a membrane transporter, sodium taurocholate cotransporting polypeptide (NTCP)
TLDR
It is reported that cyclosporin A (CsA) can inhibit HBV entry into cultured hepatocytes and provides a proof of concept for the novel strategy to identify anti‐HBV agents by targeting the candidate HBV receptor, NTCP, using CsA as a structural platform. Expand
Hepatitis B and D viruses exploit sodium taurocholate co-transporting polypeptide for species-specific entry into hepatocytes.
TLDR
Mapping of motifs in NTCPs have increased the understanding of the species specificities of HBV and HDV, and could lead to small animal models for studies of viral infection and replication. Expand
(-)-Epigallocatechin-3-gallate inhibits entry of hepatitis B virus into hepatocytes.
TLDR
Results show that the green tea-derived molecule EGCG potently inhibits HBV entry and could be used in prevention of HBV reinfection. Expand
Cyclosporin A inhibits hepatitis B and hepatitis D virus entry by cyclophilin-independent interference with the NTCP receptor.
TLDR
HBV and HDV entry via sodium taurocholate co-transporting polypeptide is inhibited by cyclosporin A and the interaction between the drug and the viral receptor is direct and overlaps with a functional binding site of the preS1 domain, which mediates viral entry. Expand
Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus
TLDR
It is shown that the receptor-binding region of pre-S1 specifically interacts with sodium taurocholate cotransporting polypeptide (NTCP), a multiple transmembrane transporter predominantly expressed in the liver that is a functional receptor for HBV and HDV. Expand
Isolation and structure of vanitaracin A, a novel anti-hepatitis B virus compound from Talaromyces sp.
TLDR
Two new tricyclic polyketides, vanitaracin A and B, together with three novel compounds 3, 4 and 5, are believed to constitute a new class of anti-HBV agents. Expand
Specific inhibition of hepatitis C virus entry into host hepatocytes by fungi-derived sulochrin and its derivatives.
TLDR
Sulochrin derivatives are anti-HCV lead compounds with a new mode of action and are the first report showing an antiviral activity of methoxybenzoate derivatives. Expand
Efficient inhibition of hepatitis B virus infection by acylated peptides derived from the large viral surface protein.
TLDR
The data shed light on the molecular mechanism of HBV entry into hepatocytes and provide a basis for the development of potent hepadnaviral entry inhibitors as a novel therapeutic concept for the treatment of hepatitis Beta. Expand
Irbesartan, an FDA approved drug for hypertension and diabetic nephropathy, is a potent inhibitor for hepatitis B virus entry by disturbing Na(+)-dependent taurocholate cotransporting polypeptide activity.
TLDR
Results suggested that irbesartan, an FDA approved drug for hypertension and diabetic nephropathy, could be a potential candidate for treatment of HBV infection although further in vivo experiments are required. Expand
Mapping of the hepatitis B virus attachment site by use of infection-inhibiting preS1 lipopeptides and tupaia hepatocytes.
TLDR
Findings indicate that the current subunit hepatitis B vaccines may be improved by the addition of distinct preS1 epitopes, and preS 1 lipopeptides are promising candidates for specific antiviral therapy against hepatitis B infections. Expand
...
1
2
3
4
5
...