title: Impact of glycoprotein B genotype and naturally occurring ORF UL56 polymorphisms upon susceptibility of clinical human cytomegalovirus isolates to letermovir.
abstract: 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.
authors.affiliation: AiCuris Anti-infective Cures GmbH, Friedrich Ebert Straße.475, 42117, Wuppertal, Germany. Electronic address: peter.lischka@aicuris.com.
authors.forename: Peter
authors.initials: P
authors.lastname: Lischka
authors.affiliation: Merck & Co., Inc, Kenilworth, NJ, USA.
authors.forename: Douglas
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Merck & Co., Inc, Kenilworth, NJ, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Holder
authors.affiliation: AiCuris Anti-infective Cures GmbH, Friedrich Ebert Straße.475, 42117, Wuppertal, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Zimmermann
mesh_terms: D000085:Acetates / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D003587:Cytomegalovirus / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D003586:Cytomegalovirus Infections / Q000821:virology*; D024882:Drug Resistance, Viral; D015774:Ganciclovir / Q000494:pharmacology; D005838:Genotype; D006801:Humans; D008826:Microbial Sensitivity Tests; D009154:Mutation; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011799:Quinazolines / Q000494:pharmacology*; D014759:Viral Envelope Proteins / Q000235:genetics*; D015678:Viral Structural Proteins / Q000235:genetics*
chemical_list: D000085:Acetates; D000998:Antiviral Agents; D011799:Quinazolines; C090238:UL56 protein, cytomegalovirus; D014759:Viral Envelope Proteins; D015678:Viral Structural Proteins; C040495:glycoprotein B, Simplexvirus; C000588473:letermovir; D015774:Ganciclovir