Phenotypic characterization of two naturally occurring human Cytomegalovirus sequence polymorphisms located in a distinct region of ORF UL56 known to be involved in in vitro resistance to letermovir
| Autor: | Thomas Goldner, Holger Zimmermann, Peter Lischka |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Human cytomegalovirus
Genotype Viral terminase complex Congenital cytomegalovirus infection Cytomegalovirus Biology Acetates medicine.disease_cause Antiviral Agents Letermovir Open Reading Frames Virology Drug Resistance Viral medicine Humans Polymerase Pharmacology Genetics Viral Structural Proteins Mutation Polymorphism Genetic Hematopoietic Stem Cell Transplantation medicine.disease Open reading frame Phenotype Cytomegalovirus Infections biology.protein Quinazolines medicine.drug |
| Zdroj: | Antiviral research. 116 |
| ISSN: | 1872-9096 |
| Popis: | Letermovir is a new drug in Phase 3 clinical development for the prevention of human Cytomegalovirus (HCMV) infections in hematopoietic-stem-cell transplant recipients (HSCT). In contrast to marketed anti-HCMV drugs which all target the viral DNA polymerase, letermovir's novel mode of action targets the UL56 subunit of the viral terminase complex. Consistently letermovir resistance has mapped in vitro to a distinct region within ORF UL56 (amino acid 230-370). Here we used marker transfer to demonstrate that two naturally occurring UL56 sequence variants within this region, located directly adjacent to sites known to mediate letermovir resistance in vitro (D242G and A327V) represent normal interstrain polymorphisms unrelated to drug-resistance. |
| Databáze: | OpenAIRE |
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