Selection and recombinant phenotyping of a novel CMX001 and cidofovir resistance mutation in human cytomegalovirus.

ABSTRACT: CMX001 is an orally available lipid acyclic nucleotide phosphonate that delivers high intracellular levels of cidofovir (CDV)-diphosphate and exhibits enhanced in vitro antiviral activity against a wide range of double-stranded DNA viruses, including cytomegalovirus (CMV). Mutations in the DNA polymerase of CMV that impart resistance to CDV also render the virus resistant to CMX001. Here, we report a novel resistance mutation that arose under the selective pressure of CMX001. The wild-type CMV strain AD169 was propagated in human foreskin fibroblasts under increasing concentrations of CMX001 over 10 months, and the resulting strain (named CMX001(R)) was less susceptible to CDV and CMX001 in a plaque reduction assay. Genotypic analysis of virus strain CMX001(R) via conventional sequencing o

SUBMITTER: James SH 

PROVIDER: S-EPMC3697342 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature