Cyclosporin A inhibits hepatitis B and hepatitis D virus entry by cyclophilin-independent interference with the NTCP receptor

Nkongolo, Shirin; Ni, Yi; Lempp, Florian A.; Kaufman, Christina L.; Lindner, Thomas; Esser-Nobis, Katharina; Lohmann, Volker; Mier, Walter; Mehrle, Stefan; Urban, Stephan

doi:10.1016/j.jhep.2013.11.022

Cited by 218 publications

(212 citation statements)

References 36 publications

Supporting

Mentioning

191

Contrasting

Unclassified

Order By: Relevance

“…Recent studies showed that cyclosporin A and its derivatives, neutralizing antibody against HBV surface protein, and compounds known to inhibit the NTCP transporter activity could inhibit HBV entry using NTCP through interfering with the binding between NTCP and the pre-S1 domain of the HBV large envelope protein (Iwamoto et al, 2014;Nkongolo et al, 2013;Watashi et al, 2013), thus, proposing a novel strategy to identify anti-HBV agents by targeting NTCP. Whether NTCP polymorphisms, including the rs2296651 polymorphism, are relevant to the action of anti-HBV agents targeting NTCP may be a focus of future investigation.…”

Section: Discussionmentioning

confidence: 99%

Association of Genetic Variation of Sodium Taurocholate Cotransporting Polypeptide with Chronic Hepatitis B Virus Infection

Zhang

Yang

et al. 2014

Genetic Testing and Molecular Biomarkers

View full text Add to dashboard Cite

Background: Sodium taurocholate cotransporting polypeptide (NTCP) plays an important role in the enterohepatic circulation of bile acids and hepatocyte function and was recently proposed to be a functional receptor for hepatitis B virus (HBV). Objective: This study investigated the association of the functional polymorphism c.800C > T (p.S267F) (rs2296651) of the NTCP gene with HBV infection. Methods: The study included 244 patients with chronic HBV infection, 76 HBV infection resolvers, and 113 healthy controls. The polymorphism was genotyped using the polymerase chain reaction-restriction fragment length polymorphism method. Results: The distribution of the genotype and allele frequency of rs2296651 polymorphism was significantly different among the HBV patients, HBV infection resolvers, and healthy controls ( p = 0.034 and p = 0.039, respectively). The frequency of genotype CT in HBV patients was significantly higher than that in healthy controls (11.9% vs. 4.4%, p = 0.026, odds ratios [OR] = 2.913, 95% confidence intervals [95% CI] = 1.097-7.738). The frequency of allele T in HBV patients was also significantly higher than that in healthy controls (5.9% vs. 2.2%, p = 0.029, OR = 2.793, 95% CI = 1.067-7.312). The frequency of genotype CT and allele T in HBV patients was higher than that in HBV infection resolvers although the difference was not significant. The genotype and allele frequency between infection resolvers and healthy controls and between HBV patients with different clinical diseases had no significant difference. Conclusion: These findings suggest that the rs2296651 polymorphism may predispose the susceptibility to and chronicity of HBV infection.

show abstract

Section: Discussionmentioning

confidence: 99%

Association of Genetic Variation of Sodium Taurocholate Cotransporting Polypeptide with Chronic Hepatitis B Virus Infection

Zhang

Yang

et al. 2014

Genetic Testing and Molecular Biomarkers

View full text Add to dashboard Cite

show abstract

“…Myrcludex-B is a lipopeptide and is therefore difficult to administer orally. To date, we and another group have reported that cyclosporine inhibits HBV infection by interrupting the interaction between LHBs and NTCP (17,35). As the immunosuppressive activity of cyclosporine was dispensable for anti-HBV activity, we showed that nonimmunosuppressive derivatives, including alisporivir, which is under clinical development for treatment of chronic hepatitis C, significantly inhibited HBV infection, suggesting that these compounds are potential anti-HBV candidates (17).…”

Section: Discussionmentioning

confidence: 74%

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

Kaneko

Watashi

Kamisuki

et al. 2015

J Virol

View full text Add to dashboard Cite

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 thatC hronic hepatitis B virus (HBV) infection, constituting a public health problem, with an estimated 240 million carriers worldwide (1), elevates the risk of development of liver cirrhosis and hepatocellular carcinoma (2). Antiviral agents against HBV include nucleos(t)ide analogs (NAs) and interferons (IFNs), which can achieve significant reductions in HBV loads (3). Although IFN-␣ and its pegylated form (peg-IFN-␣) modulate host immune responses to HBV infection or directly inhibit HBV replication in hepatocytes, these regimens show low tolerability because of serious adverse effects (3, 4). NAs, including lamivudine (LMV), adefovir, entecavir (ETV), tenofovir, and telbivudine, inhibit reverse transcription to suppress HBV replication, but longterm treatment with some of these NAs often results in selection for a significant number of drug-resistant viruses, which decreases treatment efficacy; i.e., the introduction of two substitutions, L180M and M204V, in the polymerase region leads to resistance to LMV, and an additional mutation of either T184, S202, or M250 with the L180M/M204V mutations confers further ETV resistance (5). More notably, it is difficult for the above-mentioned anti-HBV drugs to completely eliminate HBV from infected cells. Future antiviral strategies include multidrug treatment with an existing drug and a new anti-HBV agent. Consequently, there is a

show abstract

“…For HIV-1, the current model is that CypI, by blocking HIV-1 capsid-CypA interactions, prevent the nuclear import of the viral genome and its subsequent integration into the host chromosomes. For HBV, the current model is that CypI exert two independent inhibitory actions: i) an entry block, by binding to NTCP and preventing the viral glycoprotein from interacting with this cell surface receptor [63][64]; and ii) a still unknown post-entry block, likely at a transcription or translation step since CypI such as ALV inhibits HBsAg production upon HBV transfection [65]. Further work is required to fully elucidate the antiviral MoA of CypI for these three viruses.…”

Section: Discussionmentioning

confidence: 99%

Characterization of the Anti-HCV Activities of the New Cyclophilin Inhibitor STG-175

Gallay¹,

Chatterji²,

Bobardt³

et al. 2016

Journal of Hepatology

View full text Add to dashboard Cite

Cyclosporin A inhibits hepatitis B and hepatitis D virus entry by cyclophilin-independent interference with the NTCP receptor

Cited by 218 publications

References 36 publications

Association of Genetic Variation of Sodium Taurocholate Cotransporting Polypeptide with Chronic Hepatitis B Virus Infection

Association of Genetic Variation of Sodium Taurocholate Cotransporting Polypeptide with Chronic Hepatitis B Virus Infection

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

Characterization of the Anti-HCV Activities of the New Cyclophilin Inhibitor STG-175

Contact Info

Product

Resources

About