The progress of molecules and strategies for the treatment of HBV infection

Abstract

Hepatitis B virus infections have always been associated with high levels of mortality. In 2019, hepatitis B virus (HBV)-related diseases resulted in approximately 555,000 deaths globally. In view of its high lethality, the treatment of HBV infections has always presented a huge challenge. The World Health Organization (WHO) came up with ambitious targets for the elimination of hepatitis B as a major public health threat by 2030. To accomplish this goal, one of the WHO’s strategies is to develop curative treatments for HBV infections. Current treatments in a clinical setting included 1 year of pegylated interferon alpha (PEG-IFNα) and long-term nucleoside analogues (NAs). Although both treatments have demonstrated outstanding antiviral effects, it has been difficult to develop a cure for HBV. The reason for this is that covalently closed circular DNA (cccDNA), integrated HBV DNA, the high viral burden, and the impaired host immune responses all hinder the development of a cure for HBV. To overcome these problems, there are clinical trials on a number of antiviral molecules being carried out, all -showing promising results so far. In this review, we summarize the functions and mechanisms of action of various synthetic molecules, natural products, traditional Chinese herbal medicines, as clustered regularly interspaced short palindromic repeats and their associated proteins (CRISPR/Cas)-based systems, zinc finger nucleases (ZFNs), and transcription activator-like effector nucleases (TALENs), all of which could destroy the stability of the HBV life cycle. In addition, we discuss the functions of immune modulators, which can enhance or activate the host immune system, as well some representative natural products with anti-HBV effects.

Retreatment with HBV siRNA Results in Additional Reduction in HBV Antigenemia and Immune Stimulation in the AAV-HBV Mouse Model

“…A finite treatment for CHB that delivers functional cure is expected to significantly improve HBV-related morbidity and mortality, mostly by reducing the risk of developing HCC, while also removing the stigma associated with HBV infection [ 25 ]. To this effect, numerous therapeutic approaches are being investigated, both at preclinical and clinical stages, with a key objective being to reduce immune suppressive HBV antigens, particularly the HBsAg, to allow the restoration of HBV-specific immune control, through a variety of mechanisms of action and therapeutic modalities [ 10 , 26 ].…”

Prospects for Controlling Hepatitis B Globally

“…RNA interference (RNAi) molecules are used to suppress the post-transcriptional functions of HBV RNA transcripts ( Figure 4 ). Briefly, small interference RNA (siRNA) molecules or antisense oligonucleotides (ASO) are designed to contain HBV-specific complementary sequences that either destabilize or facilitate the degradation of viral transcripts upon hybridization [ 31 ].…”

Chronic Hepatitis B Infection: New Approaches towards Cure

“…Novel treatments aimed at inhibiting viral replication/antigen reduction and/or restoring host immune control are in clinical development and have been reviewed in detail by Pan et al [ 57 ]. The most advanced three classes: entry inhibitors, capsid assembly modulators, and immunomodulators are highlighted in this review.…”

“…AB-729 is a safe and well-tolerated suppressor of HBsAg and has been reported to provide robust HBV-specific T-cell restoration. In addition, RG-6346 and JNJ-3989 have proven effective in HBsAg reduction during clinical trials [ 57 ]. ALG-125755, a subcutaneous N-acetylgalactosamine (GaLNAc) conjugated HBsAg targeting siRNA, is currently in Phase I clinical trial [ 57 ].…”