NDLI: Cyclosporin A and its analogs inhibit hepatitis B virus entry into cultured hepatocytes through targeting a membrane transporter, sodium taurocholate cotransporting polypeptide (NTCP).

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Cyclosporin A and its analogs inhibit hepatitis B virus entry into cultured hepatocytes through targeting a membrane transporter, sodium taurocholate cotransporting polypeptide (NTCP).

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Cyclosporin A and its analogs inhibit hepatitis B virus entry into cultured hepatocytes through targeting a membrane transporter, sodium taurocholate cotransporting polypeptide (NTCP).

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Watashi, Koichi Sluder, Ann Daito, Takuji Matsunaga, Satoko Ryo, Akihide Nagamori, Shushi Iwamoto, Masashi Nakajima, Syo Tsukuda, Senko Borroto-Esoda, Katyna Sugiyama, Masaya Tanaka, Yasuhito Kanai, Yoshikatsu Kusuhara, Hiroyuki Mizokami, Masashi Wakita, Takaji
Description	Country affiliation: Japan Author Affiliation: Watashi K ( Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan.)
Abstract	UNLABELLED: Chronic hepatitis B virus (HBV) infection is a major public health problem worldwide. Although nucleos(t)ide analogs inhibiting viral reverse transcriptase are clinically available as anti-HBV agents, emergence of drug-resistant viruses highlights the need for new anti-HBV agents interfering with other targets. Here we report that cyclosporin A (CsA) can inhibit HBV entry into cultured hepatocytes. The anti-HBV effect of CsA was independent of binding to cyclophilin and calcineurin. Rather, blockade of HBV infection correlated with the ability to inhibit the transporter activity of sodium taurocholate cotransporting polypeptide (NTCP). We also found that HBV infection-susceptible cells, differentiated HepaRG cells and primary human hepatocytes expressed NTCP, while nonsusceptible cell lines did not. A series of compounds targeting NTCP could inhibit HBV infection. CsA inhibited the binding between NTCP and large envelope protein in vitro. Evaluation of CsA analogs identified a compound with higher anti-HBV potency, having a median inhibitory concentration <0.2 µM. CONCLUSION: This study 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.
File Format	HTM / HTML
ISSN	02709139
e-ISSN	15273350
DOI	10.1002/hep.26982
Journal	Hepatology
Issue Number	5
Volume Number	59
Language	English
Publisher	Wiley
Publisher Date	2014-05-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Hepatology Antiviral Agents Pharmacology Cyclosporine Hepatitis B Virus Drug Effects Hepatocytes Virology Organic Anion Transporters, Sodium-dependent Antagonists & Inhibitors Symporters Virus Internalization Cells, Cultured Physiology Virus Replication Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Hepatology

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Cyclosporin A and its analogs inhibit hepatitis B virus entry into cultured hepatocytes through targeting a membrane transporter, sodium taurocholate cotransporting polypeptide (NTCP)

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