Maribavir sensitivity of cytomegalovirus isolates resistant to ganciclovir, cidofovir or foscarnet

Abstract

Background: The cytomegalovirus (CMV) UL97 inhibitor drug maribavir (MBV) is undergoing clinical antiviral trials.

Objectives: To assess the MBV sensitivity of CMV strains and isolates containing mutations that confer resistance to current antiviral drugs ganciclovir, cidofovir or foscarnet.

Study design: Resistant clinical isolates and laboratory strains containing UL97 and or UL54 DNA polymerase mutations were tested for sensitivity to all four drugs by standard plaque reduction assay and a reporter-based yield reduction assay. Sensitive control strains were also tested.

Results: Eleven CMV strains or isolates resistant to GCV, four resistant to FOS and two resistant to CDV, were all sensitive to MBV. These viruses represent four UL97 mutations and three UL54 DNA polymerase mutations. The laboratory derived UL97 L397R mutant was highly MBV-resistant but remained sensitive to the other three drugs.

Conclusions: No cross-resistance has been detected between viruses resistant to MBV and those resistant to one or more of the current CMV antiviral drugs, consistent with differences in their mechanisms of action.