Successful kinase bypass with new acyclovir phosphoramidate prodrugs

Novel phosphoramidates of acyclovir have been prepared and evaluated in vitro against acyclovir-sensitive and -resistant herpes simplex virus (HSV) types 1 and 2 and varicella-zoster virus (VZV). Unlike the parent nucleoside these novel phosphate prodrugs retain antiviral potency versus the ACV-resistant virus strain, suggesting an efficient bypass of the viral thymidine kinase.

Low or sub-μM versus HSV-1 and -2 and VZV. Retain full activity versus thymidine kinase mutants proving intracellular phosphate delivery.Figure optionsDownload as PowerPoint slide