In Silico Analysis of Mechanisms of Maribavir-Induced Inhibition and Drug Resistance Mutations in pUL97 Kinase Structural Prediction with AlphaFold2.

ABSTRACT: Infections with cytomegalovirus (CMV) can result in increased morbidity and mortality in immunocompromised patients. The pUL97 kinase is a critical enzyme in the regulation of CMV replication. Although it does not phosphorylate deoxynucleosides, this enzyme is involved in the first phosphorylation step of ganciclovir (GCV), a viral DNA polymerase inhibitor. In contrast, maribavir (MBV) is a specific inhibitor of pUL97 kinase activity. In this paper, we analyzed the already-reported amino acid changes, conferring resistance to MBV and cross-resistance to GCV, in the pUL97 protein structure, predicted with AlphaFold2. Docking experiments suggest that MBV is a dual-site inhibitor, targeting ATP binding and substrate phosphorylation. Substitutions that confer resistance to MBV only may directl

SUBMITTER: Piret J 

PROVIDER: S-EPMC12301049 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature