cccDNA
HBx公司
生物
病毒学
乙型肝炎表面抗原
病毒复制
乙型肝炎病毒
HBeAg
病毒
分子生物学
作者
Purnima Tyagi,Ankita Singh,Jitendra Kumar,Belal Ahmad,Aparna Bahuguna,Perumal Vivekanandan,Shiv Kumar Sarin,Vijay Kumar
出处
期刊:Virology
[Elsevier]
日期:2024-07-01
卷期号:595: 110065-110065
标识
DOI:10.1016/j.virol.2024.110065
摘要
Nucleot(s)ide analogues, the current antiviral treatments against chronic hepatitis B (CHB) infection, are non-curative due to their inability to eliminate covalently closed circular DNA (cccDNA) from the infected hepatocytes. Preclinical studies have shown that coumarin derivatives can effectively reduce the HBV DNA replication. We evaluated the antiviral efficacy of thirty new coumarin derivatives in cell culture models for studying HBV. Furanocoumarins Fc-20 and Fc-31 suppressed the levels of pre-genomic RNA as well as cccDNA, and reduced the secretion of virions, HBsAg and HBeAg. The antiviral efficacies of Fc-20 and Fc31 improved further when used in combination with the hepatitis B antiviral drug Entecavir. There was a marked reduction in the intracellular HBx level in the presence of these furanocoumarins due to proteasomal degradation resulting in the down-regulation of HBx-dependent viral genes. Importantly, both Fc-20 and Fc-31 were non-cytotoxic to cells even at high concentrations. Further, our molecular docking studies confirmed a moderate to high affinity interaction between furanocoumarins and viral HBx via residues Ala3, Arg26 and Lys140. These data suggest that furanocoumarins could be developed as a new therapeutic for CHB infection.
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