Impact of glycoprotein B genotype and naturally occurring ORF UL56 polymorphisms upon susceptibility of clinical human cytomegalovirus isolates to letermovir

- An association between infection with a distinct HCMV gB subtype and the clinical outcome of patients has been suggested.
- Letermovir is a new anti HCMV drug in Phase 3 clinical development.
- The anti HCMV potency of letermovir is independent of the gB subtype.
- The gene region involved in letermovir resistance is highly conserved among HCMV field isolates.

Letermovir is a novel anti-HCMV drug in Phase III development that targets the UL56 subunit of the viral terminase complex. In immunocompromised patients four major glycoprotein B (gB) subtypes are known and may influence pathogenesis and thus disease outcomes. Using a panel of 74 letermovir-naïve, low-passage, clinical HCMV isolates, we examined the potential impact of i) gB genotype and ii) naturally occurring UL56 sequence variations upon susceptibility to letermovir. Our data show that letermovir's potency is independent of gB subtype and show that naturally-occurring letermovir-resistance is rare or possibly absent.