Potential Drug Targets Against Hepatitis B Virus Based on Both Virus and Host Factors

Abstract

Background: Hepatitis B is a very harmful and epidemic disease caused by hepatitis B virus (HBV). Although an effective anti-HBV vaccine is available, chronic infection poses still a huge health burden in the whole world. The present anti-HBV drugs including nucleoside analogues and interferonalpha have their limitations without exception. There is no effective drug and therapeutic method that can really and truly cure hepatitis B so far. The variability of HBV genome results in that a significant number of patients develop drug resistance during the long-term use of anti-HBV drugs. Hence, it is urgently needed to discover novel targets and develop new drugs against hepatitis B. Objective: The review aims to provide the theory support for designing of the anti-HBV innovative drugs by offering a summary of the current situation of antiviral potential targets. Results and Conclusion: Since HBV is obligate intracellular parasite, and as such it depends on host cellular components and functions to replicate itself. The targeting both virus and host might be a novel therapeutic option for hepatitis B. Accordingly, we analyse the advances in the study of the potential drug targets for anti-HBV infection, focusing on targeting virus genome, on targeting host cellular functions and on targeting virus-host proteins interactions, respectively. Meanwhile, the immune targets against chronic hepatitis B are also emphasized. In short, the review provides a summary of antiviral therapeutic strategies to target virus factors, host factors and immune factors for future designing of the innovative drug against HBV infection.

Current Status and Challenges in Anti-Hepatitis B Virus Agents Based on Inactivation/Inhibition or Elimination of Hepatitis B Virus Covalently Closed Circular DNA

“…The host factors involved in HBV cccDNA transcriptional regulation is expected to be able to provide a new approach for CHB therapy. Protein arginine methyltransferase 5 (PRMT5), as an effective restrictor of HBV transcription and replication, restricts HBV replication via a two-part mechanism, including epigenetic suppression of HBV cccDNA transcription and interference with pgRNA encapsidation [111]. These findings improved the understanding of epigenetic regulation of HBV transcription and host-HBV interactions, thus providing new insights into targeted therapeutic intervention [112].…”

“…(2) The absence of robust models for the study of HBV cccDNA due to the fact that it is difficult for HBV to infect liver cells in vitro and in vivo. (3) Direct targeting of HBV cccDNA is still a challenge, especially with no good means of blocking HBV cccDNA replication [111]. GS-080 and GS-5801 Silencing cccDNA transcription by histone lysine demethylase inhibitor.…”