Interferon (IFN) can effectively perform virological clearance in chronic hepatitis B virus (HBV) infection, but its clearance rate is low and only a few patients benefit from IFN-based therapy ( Geng et al., 2018). Our findings provided information on the development of a new class of anti-HBV agents that act on host factors rather than viral enzymes.Ĭhronic hepatitis B (CHB) is a major risk factor for liver cirrhosis and hepatocellular carcinoma ( Xia and Liang, 2019). Furthermore, the anti-HBV effect was enhanced when entecavir was administered along with either of the previous two compounds, and the effect could be blocked by knocking down EFTUD2.Ĭonclusion: We established a convenient model for screening compounds that target EFTUD2 and further identified plerixafor and resatorvid as novel HBV inhibitors in vitro. In HepAD38 cells and HBV-infected HepG2-NTCP cells, treatment with plerixafor and resatorvid strongly inhibited HBsAg, HBV DNA, HBV RNAs, and cccDNA in a dose-dependent manner. In Epro-LUC-HepG2 cells, plerixafor and resatorvid significantly upregulated the activity of the EFTUD2 promoter and the expression of the gene and protein. Results: The dual-luciferase reporter assays showed that the EFTUD2 promoter hEFTUD2pro-0.5 kb had the strongest activity. The effects of plerixafor and resatorvid on hepatitis B virus (HBV) were examined in HepAD38 cells and HBV-infected HepG2-NTCP cells. Plerixafor and resatorvid were screened from 261 immunity and inflammation-related compounds due to their ability to highly upregulate EFTUD2. Methods: In this study, we generated the Epro-LUC-HepG2 cell model for screening compounds that target EFTUD2. Previously, we had described elongation factor Tu GTP-binding domain containing 2 (EFTUD2) as an innate immune regulator and suggested that it might be an antiviral target. 4Department of Infectious and Tropical Diseases, The Second Affiliated Hospital of Hainan Medical University, Hainan, Chinaīackground: An increase in the demand for a functional cure has accelerated research on new methods of therapy for chronic hepatitis B, which is mainly focused on restoring antiviral immunity for controlling viral infections.3Department of Pediatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.2Department of Infectious Disease, Zhongda Hospital, Southeast University, Nanjing, China.11Department of Infectious Disease, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.Jinyuan Cai 1,2†, Yuwen Li 3†, Pingping Hu 2, Ruirui Xu 2, Hui Yuan 2, Wen Zhang 2, Tiantong Feng 2, Rui Liu 4, Wenting Li 4 and Chuanlong Zhu 1,4*
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