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Antimicrobial Agents and Chemotherapy, March 2009, p. 967-976, Vol. 53, No. 3
0066-4804/09/$08.00+0     doi:10.1128/AAC.00939-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Debio 025, a Cyclophilin Binding Molecule, Is Highly Efficient in Clearing Hepatitis C Virus (HCV) Replicon-Containing Cells When Used Alone or in Combination with Specifically Targeted Antiviral Therapy for HCV (STAT-C) Inhibitors{triangledown}

Lotte Coelmont,1 Suzanne Kaptein,1 Jan Paeshuyse,1 Inge Vliegen,1 Jean-Maurice Dumont,2 Grégoire Vuagniaux,2 and Johan Neyts1*

Rega Institute for Medical Research, KULeuven, Leuven 3000, Belgium,1 Debiopharm, Lausanne CP211, Switzerland2

Received 16 July 2008/ Returned for modification 13 September 2008/ Accepted 12 December 2008

Debio 025 is a potent inhibitor of hepatitis C virus (HCV) replication (J. Paeshuyse et al., Hepatology 43:761-770, 2006). In phase I clinical studies, monotherapy (a Debio 025 dose of 1,200 mg twice a day) resulted in a mean maximal decrease in the viral load of 3.6 log10 units (R. Flisiak et al., Hepatology 47:817-826, 2008), whereas a reduction of 4.6 log10 units was obtained in phase II studies when Debio 025 was combined with interferon (R. Flisiak et al., J. Hepatol., 48:S62, 2008). We here report on the particular characteristics of the in vitro anti-HCV activities of Debio 025. The combination of Debio 025 with either ribavirin or specifically targeted antiviral therapy for HCV (STAT-C) inhibitors (NS3 protease or NS5B [nucleoside and nonnucleoside] polymerase inhibitors) resulted in additive antiviral activity in short-term antiviral assays. Debio 025 has the unique ability to clear hepatoma cells from their HCV replicon when it is used alone or in combination with interferon and STAT-C inhibitors. Debio 025, when it was used at concentrations that have been observed in human plasma (0.1 or 0.5 µM), was able to delay or prevent the development of resistance to HCV protease inhibitors as well as to nucleoside and nonnucleoside polymerase inhibitors. Debio 025 forms an attractive drug candidate for the treatment of HCV infections in combination with standard interferon-based treatment and treatments that directly target the HCV polymerase and/or protease.

* Corresponding author. Mailing address: Rega Institute for Medical Research, Minderbroedersstraat 10, Leuven B-3000, Belgium. Phone: 32-16-337341. Fax: 32-16-337340. E-mail: johan.neyts{at}rega.kuleuven.be

{triangledown} Published ahead of print on 22 December 2008.

Antimicrobial Agents and Chemotherapy, March 2009, p. 967-976, Vol. 53, No. 3
0066-4804/09/$08.00+0     doi:10.1128/AAC.00939-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Chatterji, U., Bobardt, M., Selvarajah, S., Yang, F., Tang, H., Sakamoto, N., Vuagniaux, G., Parkinson, T., Gallay, P. (2009). The Isomerase Active Site of Cyclophilin A Is Critical for Hepatitis C Virus Replication. J. Biol. Chem. 284: 16998-17005 [Abstract] [Full Text]  


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