The relationship between the antiviral activity of 5'-amino-5'-deoxythymidine and its incorporation into herpes simplex virus type 1 DNA.
As part of our studies on the molecular basis for the antiherpes activity of 5'-AdThd (5'-amino-5'-deoxythymidine), a study of the HSV-1 DNA synthesized in infected Vero cells exposed to 5'-AdThd was undertaken. Unlike many other antiviral nucleoside analogs, 5'-AdThd did not inhibit HSV-1 DNA synthesis. Analysis of the DNA synthesized in the presence of [14C]5'-AdThd revealed that the analog was incorporated into the viral DNA in a dose-dependent manner and that the degree of incorporation correlated with the antiviral activity as measured by yield reduction assays. Analysis of the 5'-AdThd substituted DNA by centrifugation in neutral and alkaline sucrose gradients revealed no double-stranded breaks but an increase in single-stranded breaks, at very high concentrations of the analog. Analysis of HSV-1-specific RNAs revealed a shift from poly(A+) to poly(A-) RNA. The degree of this shift paralleled the substitution of 5'-AdThd for thymidine in the HSV-1 DNA.
D004279:DNA, Viral / Q000096:biosynthesis / Q000378:metabolism*; D015224:Dideoxynucleosides; D012367:RNA, Viral / Q000096:biosynthesis; D018139:Simplexvirus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D013936:Thymidine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
D004279:DNA, Viral; D015224:Dideoxynucleosides; D012367:RNA, Viral; C024082:5'-amino-5'-deoxythymidine; D013936:Thymidine