title: The current status and future directions of hepatitis B antiviral drug discovery.
abstract: The current standard care of chronic hepatitis B fails to induce a durable off-drug control of hepatitis B virus (HBV) replication in the majority of treated patients. The primary reasons are its inability to eliminate the covalently closed circular (ccc) DNA, the nuclear form of HBV genome, and restoration of the dysfunctional host antiviral immune response against the virus. Accordingly, discovery and development of therapeutics to completely stop HBV replication, eliminate or functionally inactivate cccDNA as well as activate a functional antiviral immune response against HBV are the primary efforts for finding a cure for chronic hepatitis B. Area covered: Herein, the authors highlight the current efforts of HBV drug discovery and offer their opinions for the future directions of this research. Expert opinion: The authors believe that through a consecutive or overlapping three-stage antiviral and immunotherapy program to: (i) completely stop HBV replication and cccDNA amplification; (ii) reduce viral antigen load and induce HBV surface antigen (HBsAg) seroclearance through eradication or inactivation of cccDNA and RNA interference-mediated degradation of viral mRNA and (iii) activate a functional antiviral immune response against HBV through therapeutic immunization or immunotherapy, a functional cure of chronic HBV infection can be achieved in the majority of chronic HBV carriers.
authors: a Microbiology and Immunology graduate program , Drexel University College of medicine , Philadelphia , PA , USA.
authors: Liudi
authors: L
authors: Tang
authors: b Baruch S. Blumberg Institute , Hepatitis B foundation , Philadelphia , PA , USA.
authors: Qiong
authors: Q
authors: Zhao
authors: b Baruch S. Blumberg Institute , Hepatitis B foundation , Philadelphia , PA , USA.
authors: Shuo
authors: S
authors: Wu
authors: b Baruch S. Blumberg Institute , Hepatitis B foundation , Philadelphia , PA , USA.
authors: Junjun
authors: J
authors: Cheng
authors: b Baruch S. Blumberg Institute , Hepatitis B foundation , Philadelphia , PA , USA.
authors: Jinhong
authors: J
authors: Chang
authors: b Baruch S. Blumberg Institute , Hepatitis B foundation , Philadelphia , PA , USA.
authors: Ju-Tao
authors: JT
authors: Guo
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D004270:DNA, Circular / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D004270:DNA, Circular; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens
keywords: Capsid assembly inhibitor; DNA polymerase inhibitor; RNA interference; cccDNA; gene editing; immunotherapy