Past, present, and future of long-term treatment for hepatitis B virus

Table 2 Mechanisms of action of the new drugs under development

Treatment class	Mechanism of action	Types
Drugs targeting HBV life cycle
Entry inhibitors	Blockage of liver-specific bile acid transporter (NTCP)	Inhibitors of NTCP[124]; NMAb[125]
Capsid assembly modulators	Interfere with capsid formation and disrupt the encapsidation of pgRNA	CAMs[126]
Post-transcriptional control inhibitors	Post-transcriptional gene silencing by inhibition of the translation of viral proteins	SiRNA[127-129]; ASOs[130,131]
HBsAg release inhibitors	Intracellular degradation of HBsAg via proteasomal and lysosomal degradation	NAPs[132,133]
Immunomodulators
Innate immune activator	Stimulation of innate immunity through TLRs and RIG-I	TLRs agonist[134-137]; RIG-I agonists[138,139]
Adaptive immune activator	Blocking the PD-1/PD-L1 pathway to reverse T-cell exhaustion; stimulation of host’s immune response to generate CD4 and CD8 HBV-specific T cells	Checkpoint inhibitors[140,141]; therapeutic vaccines[142,143]

HBV: Hepatitis B virus; NTCP: Sodium taurocholate co-transporting polypeptide; NMAb: Neutralizing monoclonal antibodies; CAMs: Nucleocapsid assembly modulators; SiRNA: Small interfering RNA; ASO: Antisense oligonucleotides; NAP: Nucleic acid polymers; TLRs: Toll-like receptors; RIG-I: Retinoic acid-inducible gene-1; PD-1: Programmed death receptor 1; PD-L1: Programmed cell death ligand 1; HBsAg: Hepatitis B virus surface antigen; HBeAg: Hepatitis B e antigen.