Current and future antiviral drug therapies of hepatitis B chronic infection

Table 1 Potential antiviral drugs for the future treatment of chronic hepatitis B virus

Potential antiviral agents	Mechanisms of action
NAs: MIV-210, elvucitabine, valtorcitabine and clevudine	Inhibition of HBV replication
Lipopeptides: Myrcludex-B	Prevention of viral entry
Disubstituted-sulfonamides: CCC-0975 and CCC-0346	Blockage of the de novo cccDNA synthesis
LTR	Destabilization cccDNA minichromosome
Zinc finger nucleases	Disruption of sequences within viral proteins
Epigenetic regulators	Repression of cccDNA transcriptional activity
Small interfering RNA	Silencing of HBV protein gene expression
Phenylpropenamides: AT-61 and AT-130	Prevention of RNA encapsidation
Heteroaryldihydropyrimidines: BAY41-4109	Nucleocapsid destabilization
Synthetic TLR-7 agonists	Inhibition of HBV replication via pDC activation
IL8 inhibitors	Increase the potency of IFN-α treatment
REP 9AC amphipathic polymers	Inhibition of subviral particles
Inhibitors of PD-1 and TIM3 receptors	Restoration of T cell function
Immunization with DC pulsed with HBV antigens	Induction of viral specific CTLs
Therapeutic vaccines containing viral peptides	Induction HBV-specific responses
Cytokines: IL12, IL2, IFNγ and TNF-α	Restoration of HBV specific T cell activity
Thymosin alpha polypeptide	Induction of T cell function and NK cytotoxicity

cccDNA: Covalently closed circular DNA; CTLs: Cytotoxic T lymphocytes; DC: Dendritic cells; HBV: Hepatitis B virus; MIV: Lagociclovir valactate; NK: Natural killer; pDC: Plasmacytoid DCs; PD-1: Programmed cell death 1; TLR: Toll like receptor; TIM3: T-cell immunoglobulin domain mucin domain-containing molecule-3; IFN: Interferon; TNF: Tumor necrosis factor; NAs: Nucleos(t)ide analogues; LTR: Lymphotoxin receptor; IL: Interleukin.