Host-targeting agents for treatment of hepatitis B virus infection

Hepatitis B virus: is a cure possible?

“…The recent progress in our understanding of the virus-host interactions governing HBV infection combined with technological progress has enabled a new era for the study of HBV infection as well as for the design of novel antiviral strategies [4,5,9,10]. This has led to the awareness among basic researchers and clinicians that close collaborations are required on national and international levels in order to develop a cure for HBV [4,7].…”

“…Although several breakthroughs have been achieved within the past years, further basic and translational studies are required to evaluate the best approaches to ultimately cure chronic HBV infection. The complexity of the virus life cycle and the ability of the virus to persist as cccDNA enabling its reactivation have long hampered the development of novel antivirals and suggest that combination(s) of several strategies may be required to achieve this goal [4,5,9,10]. Based on recent scientific progress of the last years, novel therapeutic strategies aiming at functional cure are currently entering clinical evaluation.…”

“…phenylpropenamide derivatives, heteroaryldihydropyrimidines) that decrease nucleocapsid assembly/stability, and small interfering RNA-based strategies (e.g. ARC-520 and ISIS-HBVRx) aiming at viral RNA degradation [4,5,7,[9][10][11].…”

“…REP 9 AC) [4,5,7,9,10,12,13]. Other strategies aim at promoting the elimination of infected hepatocytes by restoring antiviral immunity using immunomodulatory compounds (e.g.…”

“…Other strategies aim at promoting the elimination of infected hepatocytes by restoring antiviral immunity using immunomodulatory compounds (e.g. TLR7 agonists) or antigen-or DNA-based therapeutic vaccines as well as by tumor necrosis factor-mediated killing of HBV-infected hepatocytes using antagonists of cellular inhibitors of apoptosis proteins [4,5,7,[9][10][11][14][15][16]. Interestingly, given that long-term NUC treatment can restore T-cell responses in chronic hepatitis B patients, increasing antiviral T-cell responses by immunotherapeutic strategies might increase the chances of achieving control of HBV infection [17].…”