guanosine-triphosphate and Hepatitis-B

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. 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.. In this study, we generated the Epro-LUC-HepG2 cell model for screening compounds that target EFTUD2. Plerixafor and resatorvid were screened from 261 immunity and inflammation-related compounds due to their ability to highly upregulate EFTUD2. The effects of plerixafor and resatorvid on hepatitis B virus (HBV) were examined in HepAD38 cells and HBV-infected HepG2-NTCP cells.. The dual-luciferase reporter assays showed that the EFTUD2 promoter hEFTUD2pro-0.5 kb had the strongest activity. In Epro-LUC-HepG2 cells, plerixafor and resatorvid significantly upregulated the activity of the EFTUD2 promoter and the expression of the gene and protein. 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. 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.. We established a convenient model for screening compounds that target EFTUD2 and further identified plerixafor and resatorvid as novel HBV inhibitors

Topics: Antiviral Agents; DNA, Viral; Guanosine Triphosphate; Hematopoietic Stem Cell Mobilization; Hep G2 Cells; Hepatitis B; Hepatitis B virus; Heterocyclic Compounds; Humans; Peptide Elongation Factor Tu; Peptide Elongation Factors; Ribonucleoprotein, U5 Small Nuclear; Virus Replication

The elongation factor Tu GTP-binding domain-containing 2 gene (. In total, 448 control subjects and 379 patients with chronic HBV infection from Zhangjiagang First People's Hospital (Jiangsu, China) were enrolled. Sequenom iPLEX assay was used to detect genotypes of four SNPs (rs1071682, rs2277617, rs2289674, and rs3809756). Dual-luciferase reporter vectors with wild-type A and mutant-type C alleles of. Only rs3809756 was significantly associated with HBV infection susceptibility (

Topics: Alleles; Case-Control Studies; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Guanosine Triphosphate; Hepatitis B; Hepatitis B virus; Hepatitis B, Chronic; Humans; Male; Peptide Elongation Factor Tu; Peptide Elongation Factors; Polymorphism, Single Nucleotide; Ribonucleoprotein, U5 Small Nuclear