Effects of Maribavir on Ganciclovir Resistant Cytomegalovirus
Author Information
Author(s): Shannon-Lowe Claire D, Emery Vincent C
Primary Institution: Department of Infection, Centre for Virology, UCL (Royal Free Campus), London, UK
Hypothesis
How does maribavir affect the autophosphorylation of ganciclovir resistant mutants of the cytomegalovirus UL97 protein?
Conclusion
Maribavir is a potent competitive inhibitor of the UL97 protein kinase and shows increased activity against the M460I GCV-resistant mutant.
Supporting Evidence
- Maribavir inhibited autophosphorylation of wild type and major GCV resistant UL97 mutants.
- The M460I mutation showed hypersensitivity to maribavir with an IC50 of 4.8 nM.
- Maribavir was shown to be a competitive inhibitor of ATP with a Ki of 10 nM.
Takeaway
Maribavir helps fight a virus that is resistant to a common drug by blocking a key protein it needs to work.
Methodology
Recombinant baculoviruses were used to express wild type and mutant UL97 proteins, which were then analyzed for their autophosphorylation and GCV phosphorylation activities in the presence of maribavir.
Limitations
The study primarily focused on specific UL97 mutations and may not encompass all possible mutations affecting drug resistance.
Statistical Information
P-Value
0.01
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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