Drug Susceptibility and Replicative Capacity of Multi-Drug Resistant Recombinant Human Cytomegalovirus Harboring Mutations in UL56 and UL54 Genes [PublishAheadOfPrint]

Letermovir is an investigational antiviral agent with a novel mechanism of action involving the viral terminase (pUL56). We evaluated the impact of V236M mutation in UL56 gene alone and combined with E756K mutation in UL54 gene on drug susceptibility and viral replicative capacity of recombinant human cytomegalovirus. The double mutant exhibited at least borderline resistance to all antivirals tested (ganciclovir, foscarnet, cidofovir, brincidofovir and letermovir) and replicated less efficiently than the wild-type virus in vitro.

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