title: Development of novel hepatitis B virus capsid inhibitor using in silico screening.
abstract: Antiviral therapy for chronic hepatitis B that uses nucleos(t)ide analogue is considered effective. However, most drugs of this class frequently result in viral relapse after cessation of therapy as well as the emergence of resistance, thereby limiting their clinical use. In order to increase the therapeutic efficiency of chronic hepatitis B treatments, it is important to survey novel (chemical) reagents targeting other stages of the viral replication process. The aim of this study was to identify novel capsid inhibitor candidates using in silico screening. We discovered four such candidates that decreased the levels of HBV DNA and HBsAg in vitro. These four capsid inhibitor candidates did not induce cell toxicity even at high concentrations. Results from docking simulation showed that the candidates bounded with high affinity with the capsid protein hydrophobic binding site. Identifying direct acting HBV core protein inhibitors increases the likelihood that novel medicines can be developed that allows the combination of novel anti-viral drugs and nucleos(t)ide analogue or interferon for HBV treatment.
authors.affiliation: Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka 545-8585, Japan.
authors.forename: Michiyo
authors.initials: M
authors.lastname: Hayakawa
authors.affiliation: Department of Biological Science, Chuo University, Tokyo 112-8551, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Umeyama
authors.affiliation: Department of Biological Science, Chuo University, Tokyo 112-8551, Japan.
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Iwadate
authors.affiliation: Department of Medical Pharmaceutics, Kobe Pharmaceutical University, Kobe 650-0017, Japan.
authors.forename: Toshihito
authors.initials: T
authors.lastname: Tanahashi
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Yano
authors.affiliation: Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka 545-8585, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Enomoto
authors.affiliation: Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka 545-8585, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tamori
authors.affiliation: Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka 545-8585, Japan.
authors.forename: Norifumi
authors.initials: N
authors.lastname: Kawada
authors.affiliation: Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka 545-8585, Japan. Electronic address: m2079633@med.osaka-cu.ac.jp.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Murakami
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D002213:Capsid / Q000187:drug effects*; D003198:Computer Simulation; D004279:DNA, Viral / Q000235:genetics; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D062105:Molecular Docking Simulation
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral
keywords: Capsid inhibitor; Hepatitis B virus; In silico screening