Targeting hepatitis B virus cccDNA levels: Recent progress in seeking small molecule drug candidates

PreS1BP mediates inhibition of Hepatitis B virus replication by promoting HBx protein degradation

“…The HBV infection process begins with the pre-S1 region of the viral surface protein binding to the sodium taurocholate co-transporting polypeptide (NTCP) on hepatocytes ( Schulze et al., 2007 ; Yan et al., 2012 ), initiating endocytic viral entry. Upon internalization and envelope removal, the viral capsids are transported to the nucleus, where relaxed circular DNA (rcDNA) is converted into covalently closed circular DNA (cccDNA), serving as a transcriptional template for viral RNAs, including pregenomic RNA (pgRNA) ( Jiang and Hildt, 2020 ; Jin et al., 2023 ). This pgRNA is instrumental in the synthesis of viral antigens and replication within host cells ( Wang et al., 2016 ).…”

“…Eradication of CHB remains elusive, primarily due to the persistence of cccDNA within infected cells ( Jin et al., 2023 ). The HBV genome's compact nature encodes four overlapping reading frames, producing the core, polymerase, surface, and X (HBx) canonical proteins.…”