Inhibition of hepatitis B virus replication by drug-induced depletion of nucleocapsids.
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.
Deres
Karl
K
Department of Virology, Chemistry, Isotope Chemistry, Preclinical Pharmakokinetics, Toxicology, Safety Pharmacology, Bayer Research Center, Wuppertal, Germany. karl.deres.kd1@bayer-ag.de
Schröder
Claus H
CH
Paessens
Arnold
A
Goldmann
Siegfried
S
Hacker
Hans Jörg
HJ
Weber
Olaf
O
Krämer
Thomas
T
Niewöhner
Ulrich
U
Pleiss
Ulrich
U
Stoltefuss
Jürgen
J
Graef
Erwin
E
Koletzki
Diana
D
Masantschek
Ralf N A
RN
Reimann
Anja
A
Jaeger
Rainer
R
Gross
Rainer
R
Beckermann
Bernhard
B
Schlemmer
Karl-Heinz
KH
Haebich
Dieter
D
Rübsamen-Waigmann
Helga
H
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
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