3,7-Dihydroxytropolones Inhibit Initiation of Hepatitis B Virus Minus-Strand DNA Synthesis
Abstract
:1. Introduction
2. Results
2.1. Establishing the HBV Minus-Strand DNA Priming System
2.2. Small Molecules that Recognize HBV Epsilon Do not Inhibit Priming
2.3. 3,7 Dihydroxytropolones Inhibit HBV (-) Strand DNA Synthesis
2.4. 3,7-dHTs Inhibit Covalent Attachment of dGTP to HBV P Protein
2.5. 3,7-dHTs Inhibit Priming by an RNase H-Deficient HBV Polymerase
2.6. Activity of Non-Troponoid Nucleotidyltransferase Inhibitors
2.7. 3,7-dHT 196 Does Not Induce Dissociation of the HBV Initiation Complex
2.8. Modeling Supports Additional Interactions of 3,7-dHTs at the HBV Polymerase Active Site
3. Discussion
4. Materials and Methods
4.1. α–HTs and 3,7-dHTs
4.2. Plasmids
4.3. Protein, RNA Expression and Purification
4.4. In Vitro Protein Priming
4.5. In Vitro Binding of ε RNA to HBV Polymerase
4.6. HBV ε RNA Detection
4.7. Modeling Ligand Binding within the HBV Polymerase Active Site
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Sample Availability: Samples of the compounds are not available from the authors. |
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Bak, E.; Miller, J.T.; Noronha, A.; Tavis, J.; Gallicchio, E.; Murelli, R.P.; Le Grice, S.F.J. 3,7-Dihydroxytropolones Inhibit Initiation of Hepatitis B Virus Minus-Strand DNA Synthesis. Molecules 2020, 25, 4434. https://doi.org/10.3390/molecules25194434
Bak E, Miller JT, Noronha A, Tavis J, Gallicchio E, Murelli RP, Le Grice SFJ. 3,7-Dihydroxytropolones Inhibit Initiation of Hepatitis B Virus Minus-Strand DNA Synthesis. Molecules. 2020; 25(19):4434. https://doi.org/10.3390/molecules25194434
Chicago/Turabian StyleBak, Ellen, Jennifer T. Miller, Andrea Noronha, John Tavis, Emilio Gallicchio, Ryan P. Murelli, and Stuart F. J. Le Grice. 2020. "3,7-Dihydroxytropolones Inhibit Initiation of Hepatitis B Virus Minus-Strand DNA Synthesis" Molecules 25, no. 19: 4434. https://doi.org/10.3390/molecules25194434
APA StyleBak, E., Miller, J. T., Noronha, A., Tavis, J., Gallicchio, E., Murelli, R. P., & Le Grice, S. F. J. (2020). 3,7-Dihydroxytropolones Inhibit Initiation of Hepatitis B Virus Minus-Strand DNA Synthesis. Molecules, 25(19), 4434. https://doi.org/10.3390/molecules25194434