Hepatitis B virus (HBV) capsid assembly modulators (CAMs) represent a promising therapeutic approach in the treatment of chronic HBV infection. In the quest for effective therapeutics against chronic Hepatitis B virus (HBV) infection, we employed a novel binding site occupancy strategy to develop novel 2-cyclopropyl-thioureidobenzamide (CP-TBA) derivatives as potent HBV CAMs. Our diversity modification approach led to the identification of compound 17e, which demonstrated remarkable anti-HBV activity with an EC of 0.
View Article and Find Full Text PDFT cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) is an immune checkpoint that has critical roles in immune exhaustion. However, little is known about the mechanisms that regulate TIM-3 surface expression and turnover. Here, we report that human TIM-3 is palmitoylated by the palmitoyltransferase DHHC9 at residue cysteine 296 (Cys).
View Article and Find Full Text PDFHepatitis B virus (HBV) covalently closed circular DNA (cccDNA) contributes to viral persistence and recurrence, however, how the host innate immune system responds to cccDNA is still less known. Here, based on cccDNA-hepatic proteins interaction profiling, DNA sensor ATP-binding cassette subfamily F member 1 (ABCF1) is identified as a novel cccDNA-binding protein and host restriction factor for HBV replication. Mechanistically, ABCF1 recognizes cccDNA by KKx4 motif and forms phase-separated condensates by the poly-glutamine (PolyQ) region of the N-terminal intrinsically disordered low-complexity domain (LCD).
View Article and Find Full Text PDFHepatitis B virus (HBV) capsid assembly modulators (CAMs) represent a promising therapeutic approach for the treatment of HBV infection. In this study, we designed and synthesized five series of benzamide derivatives based on a multisite-binding strategy at the tolerant region and diversity modification in the solvent-exposed region. Among them, thioureidobenzamide compound exhibited significantly increased anti-HBV activity in HepAD38 (EC = 0.
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