File:Viruses-14-00701-g001-550.webp

English: Figure 1. HBV replicative cycle and targets of the drugs under development to cure chronic hepatitis B patients. Description of their mode of action at the different steps of the HBV cycle or according to their modulation of immune response: (1) inhibition of viral entry by Na-Taurocholate Cotransporting Polypeptide (NTCP) receptor inhibitors or by neutralizing antibodies targeting the Pre-S1 domain of the HBsAg (b); (2) destabilization/degradation of the nuclear covalently closed circular DNA (cccDNA) or inhibition of its transcription; (3) inhibition of viral proteins synthesis by targeting viral mRNAs coding for HBx, small, middle and large (S, M and L) HBs, Core and Polymerase (Pol) proteins; (4) interference with Core protein assembly and (5) HBcAg-mediated cccDNA replenishment; (6) inhibition of viral and subviral particles HBsAg release; (a) modulation of innate immunity by Toll Like Receptors (TLR) agonists, which can activate Plasmacytoid Dendritic Cells (PDC), Natural Killer (NK) cells, or Interferon (IFN) Sensitive Genes (ISGs) response, which increase the production of several IFN Response Factors (IRFs) with broad-spectrum antiviral activity, similar to that of 2′-5′-oligoadenylate synthetase (OASs) and RNase L; (b) modulation of the adaptive immunity, by check point inhibitors acting on the Programmed Death 1 (PD-1) receptor of viral antigen-specific T cells exhausted because of the antigen overload, thus improving Cytotoxic T Lymphocytes (CTL) activity. Alternative approaches to increase recognition and elimination of HBV infected cells include genetically engineered T cells and therapeutic vaccines.