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Semin Liver Dis 2019; 39(01): 078-085
DOI: 10.1055/s-0038-1676804
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Concept of Viral Inhibitors via NTCP

Kento Fukano   *
1   Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan
2   Department of Analytical Biochemistry, Meiji Pharmaceutical University, Kiyose, Japan
,
Senko Tsukuda   *
1   Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan
3   Liver Cancer Prevention Research Unit, RIKEN Center for Integrative Medical Sciences (IMS), Wako, Japan
,
Koichi Watashi
1   Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan
4   Department of Applied Biological Science, Tokyo University of Science, Noda, Japan
5   JST CREST, Saitama, Japan
,
Takaji Wakita
1   Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan
› Author Affiliations
Funding This study was supported by the Japan Society for the Promotion of Science KAKENHI (JP17H04085, JP66KT0111, JP16K19145); the JST CREST program; the Japan Agency for Medical Research and Development, AMED (JP18fk0310114j0002, JP18fk0310101j1002, JP18fk0310103j0202, JP18fm0208019j0002, JP18fk0210036j0001, 18fm0208019h0202); the Takeda Science Foundation; the MSD Life Science Foundation; the Pharmacological Research Foundation, Tokyo; and the Japan Food Chemical Research Foundation, Tokyo.
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Publication History

Publication Date:
17 January 2019 (online)

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Abstract

Identification of sodium taurocholate cotransporting polypeptide (NTCP) as an entry receptor for hepatitis B and D viruses (HBV and HDV) has not only promoted our understanding of the mechanism underlying the viral entry process, but also provided cell culture models supporting viral infection. These models have greatly facilitated cell-based chemical screening for the discovery of entry inhibitors, and mode of action studies using such inhibitors have shown the advantages of NTCP as a drug target. Furthermore, 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. This review summarizes this hot topic in the development of HBV/HDV entry inhibitors, with special focus on the use of NTCP as a drug target.

Keywords

HBV - HDV - NTCP - entry - screening

* These authors contributed equally to this work.