New antivirals for the treatment of chronic hepatitis B

Abstract

Current treatment with oral nucleos(t)ides entecavir or tenofovir provide sustained suppression of HBV replication and clinical benefit in most chronic hepatitis B virus (HBV) infected persons. However, HBV rebound generally occurs upon drug discontinuation due to persistence of genomic HBV reservoirs as episomic cccDNA and chromosomic integrated HBV-DNA. There is renewed enthusiasm on HBV drug discovery following recent successes with antivirals for hepatitis C and immunotherapies for some cancers. Areas covered: New drugs that target distinct steps of the HBV life cycle are been developed, including inhibitors of viral entry, new polymerase inhibitors, capsid and assembly inhibitors, virus release blockers, and disruptors of cccDNA formation and transcription. Alongside these antivirals, agents that enhance anti-HBV specific immune responses are being tested, including TLR agonists, checkpoint inhibitors and therapeutic vaccines. Expert opinion: The achievement of a 'functional cure' for chronic HBV infection, with sustained HBsAg clearance and undetectable viremia once medications are stopped, represents the next step in the pace towards HBV elimination. Hopefully, the combination of new drugs that eliminate or functionally inactivate the genomic HBV reservoirs (cccDNA and integrated HBV-DNA) along with agents that enhance or activate immune responses against HBV will lead to a 'definitive cure' for chronic HBV infection.

Viral hepatitis

“…These are targeted at different stages of the viral life cycle, including inhibitors of viral entry into the cell, capsid and viral assembly inhibitors and disruptors of ccc DNA. The agents are currently in phases 2 and 3 clinical trials …”

Hepatitis B virus S gene therapy with 10-23 DNAzyme delivered by chitosan-g-stearic acid micelles

“…The achievement of a 'functional cure' for chronic HBV infection with sustained HBsAg clearance, represents the next step in the pace towards HBV elimination. 15 The discovery of DNAzymes breaks the traditional concept of protease-based biocatalysts. A DNAzyme is a structured DNA sequence with catalytic RNA-cleaving activity.…”

Baracle^® vs Baraclude^® for 48 weeks in patients with treatment-naïve chronic hepatitis B: a comparison of efficacy and safety

“…ETV-triphosphate exerts antiviral effects by inhibiting three steps of replication: priming of HBV DNA polymerase, reverse transcription of the HBV DNA negative strand from pregenomic mRNA, and synthesis of the HBV DNA positive strand. 7 , 8 …”