Copyright ©The Author(s) 2022.
World J Virol. Jan 25, 2022; 11(1): 57-72
Published online Jan 25, 2022. doi: 10.5501/wjv.v11.i1.57
Table 1 Developing new therapeutic drug targets for chronic hepatitis B
Mechanism of action
Therapeutic class
Route of administration
Clinical trial
HBV entry inhibitors
Bulevirtide (Myrcludex B)[49]Competition with NTCPPeptideSubcutaneous injectionIIbHBsAg loss in 27% of HBV/HDV co-infected patients after 48 wk of treatment with Bulevirtide + pegIFN-α and 24 wk treatment-free follow-up
cccDNA disruptors
CRISPR/Cas9[67]Disruption of cccDNAGene editingIn vivoPre-clinicalSignificantly improved survival of human hepatocytes in liver-humanized FRG mice and demonstrated a decreasing of total liver HBV-DNA and cccDNA
ZFNs[69]Disruption of cccDNAGene editingIn vitroPre-clinicalEfficiently suppress the cellular template for HBV persistence and inhibit active HBV replication
Nucleocapsid assembly modulators
JNJ-632 and BAY41-4109[73]Misdirecting the formation of capsid-like structuresCapsid assembly modulatorsIn vitroPre-clinicalInduce the formation of morphologically intact viral capsids and prevented formation of cccDNA
NVR3-778[78]Misdirecting the formation of capsid-like structuresCapsid assembly modulatorIn vivoI/IIThe largest mean reduction in serum HBV DNA levels was achieved from the combination treatment of 600 mg NVR3-778 BD + pegIFN 180 mg subcutaneous weekly (1.97 log10 IU/mL)
JNJ-6379[76]Misdirecting the formation of capsid-like structuresCapsid assembly modulatorsOralIINo clinically significant changes in levels of HBsAg were observed
ABI-H0731[77]Misdirecting the formation of capsid-like structuresCapsid assembly modulatorsOralI/IIDose-dependent reduces in HBV DNA and HBV RNA not HBsAg was seen in both HBeAg-positive and HBeAg-negative patients
HBV transcription inhibitors
ARC-520[84]Interference viral mRNATranscription inhibitorIntravenous injectionIICHB patients with high dose significantly reduced HBsAg and persisted for > 85 d after the last dose
GSK3389404[85]Interference viral mRNATranscription inhibitorSubcutaneous injectionIDose 120 mg for 4 wk was safe and well tolerate
RG7834[87]Interference viral mRNAGene expression inhibitorIn vivoPre-clinicalReduced WHsAg by a mean of 2.57 log10 and WHV DNA by a mean of 1.71 log10 from baseline. However, WHsAg and WHV DNA rebounded to baseline after stopped treatment and WHsAb was not observed.
HBsAg release inhibitors
REP 2055 and REP 2139-Ca[88]HBsAg release inhibitorsNAPsIntravenous injectionIISubstantially reduction of HBsAg levels, HBV DNA levels and increasing of serum HBsAb
REP 2139-Mg and REP 2165-Mg[90]HBsAg release inhibitorsNAPsIntravenous injectionIIAddition of NAPs to TDF + pegINFα-2a significantly increased rates of HBsAg loss during therapy and functional cure after therapy