title: Inhibition of hepatitis B virus replication by drug-induced depletion of nucleocapsids.
abstract: 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.
authors.affiliation: Department of Virology, Chemistry, Isotope Chemistry, Preclinical Pharmakokinetics, Toxicology, Safety Pharmacology, Bayer Research Center, Wuppertal, Germany. karl.deres.kd1@bayer-ag.de
authors.forename: Karl
authors.initials: K
authors.lastname: Deres
authors.forename: Claus H
authors.initials: CH
authors.lastname: Schröder
authors.forename: Arnold
authors.initials: A
authors.lastname: Paessens
authors.forename: Siegfried
authors.initials: S
authors.lastname: Goldmann
authors.forename: Hans Jörg
authors.initials: HJ
authors.lastname: Hacker
authors.forename: Olaf
authors.initials: O
authors.lastname: Weber
authors.forename: Thomas
authors.initials: T
authors.lastname: Krämer
authors.forename: Ulrich
authors.initials: U
authors.lastname: Niewöhner
authors.forename: Ulrich
authors.initials: U
authors.lastname: Pleiss
authors.forename: Jürgen
authors.initials: J
authors.lastname: Stoltefuss
authors.forename: Erwin
authors.initials: E
authors.lastname: Graef
authors.forename: Diana
authors.initials: D
authors.lastname: Koletzki
authors.forename: Ralf N A
authors.initials: RN
authors.lastname: Masantschek
authors.forename: Anja
authors.initials: A
authors.lastname: Reimann
authors.forename: Rainer
authors.initials: R
authors.lastname: Jaeger
authors.forename: Rainer
authors.initials: R
authors.lastname: Gross
authors.forename: Bernhard
authors.initials: B
authors.lastname: Beckermann
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Schlemmer
authors.forename: Dieter
authors.initials: D
authors.lastname: Haebich
authors.forename: Helga
authors.initials: H
authors.lastname: Rübsamen-Waigmann
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D002213:Capsid / Q000378:metabolism; D004261:DNA Replication / Q000187:drug effects; D004279:DNA, Viral / Q000096:biosynthesis; D006207:Half-Life; D015611:Hepatitis B Virus, Duck / Q000187:drug effects / Q000378:metabolism; D006515:Hepatitis B virus / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D009154:Mutation; D019251:Nucleocapsid / Q000378:metabolism*; D011725:Pyridines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011743:Pyrimidines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000378:metabolism; D013237:Stereoisomerism; D014230:Triazoles / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014758:Viral Core Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019065:Virus Assembly / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; C472015:BAY 38-7690; C472016:BAY 39-5493; C464059:BAY 41-4109; D004279:DNA, Viral; D011725:Pyridines; D011743:Pyrimidines; D011994:Recombinant Proteins; D014230:Triazoles; D014758:Viral Core Proteins; C067713:lactacystin; D000111:Acetylcysteine