Codex_V5

Comparison of Cytomegalovirus Terminase Gene Mutations Selected after Exposure to Three Distinct Inhibitor Compounds.

Abstract: Letermovir, GW275175X (a benzimidazole), and tomeglovir (Bay38-4766) are chemically unrelated human cytomegalovirus (CMV) terminase complex inhibitors that have been tested in human subjects. UL56 gene mutations are the dominant pathway of letermovir resistance, while UL89 and UL56 mutations are known to confer benzimidazole resistance. This study compares the mutations elicited by the three inhibitors during

Mutant	Gene	Virus	Antiviral	EC50 ratio	Phenotype
N232Y	UL56	Human betaherpesvirus 5	Letermovir	17.00	High level resistance
K258E	UL56	Human betaherpesvirus 5	Letermovir	14.00	High level resistance
N320H	UL89	Human betaherpesvirus 5	Letermovir	1.80	No resistance
N329S	UL89	Human betaherpesvirus 5	Letermovir	2.00	Low level resistance
D344E	UL89	Human betaherpesvirus 5	Letermovir	1.80	No resistance
T350M	UL89	Human betaherpesvirus 5	Letermovir	2.80	Low level resistance