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Science 299 (5608): 893-896

Copyright © 2003 by the American Association for the Advancement of Science

Inhibition of Hepatitis B Virus Replication by Drug-Induced Depletion of Nucleocapsids

Karl Deres,1*dagger Claus H. Schröder,7*dagger Arnold Paessens,1dagger Siegfried Goldmann,2 Hans Jörg Hacker,7 Olaf Weber,8 Thomas Krämer,2 Ulrich Niewöhner,2 Ulrich Pleiss,3 Jürgen Stoltefuss,2 Erwin Graef,1 Diana Koletzki,1 Ralf N. A. Masantschek,1 Anja Reimann,7 Rainer Jaeger,5 Rainer Groß,6 Bernhard Beckermann,4 Karl-Heinz Schlemmer,4 Dieter Haebich,2 Helga Rübsamen-Waigmann1dagger

Chronic hepatitis B virus (HBV) infection is a major cause of liver disease. Only interferon-alpha and the nucleosidic inhibitors of the viral polymerase, 3TC and adefovir, are approved for therapy. However, these therapies are limited by the side effects of interferon and the substantial resistance of the virus to nucleosidic inhibitors. Potent new antiviral compounds suitable for monotherapy or combination therapy are highly desired. We describe non-nucleosidic inhibitors of HBV nucleocapsid maturation that possess in vitro and in vivo antiviral activity. These inhibitors have potential for future therapeutic regimens to combat chronic HBV infection.

Department of 1 Virology, 2 Chemistry, 3 Isotope Chemistry, 4 Preclinical Pharmakokinetics, 5 Toxicology, 6 Safety Pharmacology, Bayer Research Center, Wuppertal, Germany. 7 Deutsches Krebsforschungszentrum, Virus-Host-Interactions, Heidelberg, Germany. 8 Bayer Corporation, Pharmaceutical Division, 400 Morgan Lane, West Haven, CT 06516-4175, USA.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: karl.deres.kd1{at}bayer-ag.de (K.D.); c.schroeder{at}dkfz.de (C.H.S.); arnold.paessens.ap{at}bayer-ag.de (A.P.); helga.ruebsamen-waigmann.hr{at}bayer-ag.de (H.R.-W.)

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