Hepatitis B is a liver infection caused by the hepatitis B virus (HBV). HBV is transmitted when blood, semen, or another body fluid from a person infected with virus enters the body of someone who is not infected. This can happen through sexual contact; sharing needles, syringes, or other drug-injection equipment; or from mother to baby at birth.
For some people, hepatitis B is a short-term illness, but for others, it can become a long-term, chronic infection. Risk for chronic infection is related to age at infection: approximately 90% of infected infants become chronically infected, compared with 2%–6% of adults. Chronic hepatitis B can lead to serious health issues, like cirrhosis or liver cancer. The best way to prevent hepatitis B is by getting vaccinated.
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NVR 3-778 (NVR3-778, NVR 3778) is a small molecule inhibitor of HBV replication that targets the viral core protein, a first-in-class capsid assembly modulator; inhibits the generation of infectious HBV DNA containing virus particles with EC50 of 0.40 uM in HepG2.2.15 cells; NVR 3-778 inhibits pgRNA encapsidation, viral replication and the production of HBV DNA- and HBV RNA-containing particles, also inhibits de novo infection and viral replication in primary human hepatocytes with EC50 of 0.81 uM against HBV DNA and 3.7-4.8 uM against the production of HBV antigens and intracellular HBV RNA; demonstrates favorable pharmacokinetics and safety in animal species.
Inarigivir soproxil (SB-9200, SB9200, Inarigivir, ORI-9020) is an orally bioavailable dinucleotide that activates RIG-I and NOD2, induces interferon mediated antiviral immune responses; shows broad-spectrum antiviral activity against RNA viruses including HCV, norovirus, RSV and influenza, and also demonstrates activity HBV in vitro and in vivo; a novel agonist of innate immunity, and prodrug of Inarigivir (ORI-9020;SB-9000).
Morphothiadin(GLS4) is a potent inhibitor of HBV capsid assembly, inhibits HBV replication (EC50=62.24 nM) and reduces HBV-DNA levels in HepG.2.2.15 cells (IC50=14 nM), shows efficacy against ADV-resistant HBV mutations; strongly inhibits core gene expression (at 100 to 200 nM), suppresses virus accumulation in the supernantant of HepAD38 cells; inhibits HBV replicative forms in the live, shows strong and sustained suppression of virus DNA in treated mice.
AB-423 is a novel potent, class II HBV capsid inhibitor that shows potent inhibition of HBV replication with EC50 of 0.08-0.27 uM, with no significant cytotoxicity (CC50>10 uM); inhibits HBV genotypes A through D and nucleos/tide-resistant variants, causes capsid particles devoid of encapsidated pgRNA and rcDNA in treated HepDES19 cells, prevents the conversion of encapsidated rcDNA to cccDNA presumably by interfering with the capsid uncoating process; dose-dependently reduces serum HBV DNA levels in mouse model of HBV model, shows synergistic antiviral activity combined with entecavir (ETV).
RO6889678(RO 6889678) is a highly potent inhibitor of HBV capsid formation with attributes that are favorable for targeting the liver, whilst maintaining moderate peripheral exposure.
Isothiafludine (NZ-4) is a novel HBV capsid assembly inhibitor that inhibits HBV replication through blocking pregenomic RNA encapsidation, suppresses HBV replication in HepG2.2.15 cells with IC50 of 1.33 uM; shows activity against the replication of various drug-resistant HBV mutants, including 3TC/ETV-dual-resistant and ADV-resistant HBV mutants; concentration-dependently reduces the encapsidated HBV pgRNA, resulting in the assembly of replication-deficient capsids in HepG2.2.15 cells; inhibits DHBV DNA replication in the DHBV-infected ducks after oral administration.
Besifovir (PMCDG Dipivoxil, NA-380, LB-80380) is a potent, selective, orally available anti-HBV agent, the prodrug of PMCDG (EC50=4 uM).
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