The sensitivity of acyclovir-resistant mutants of herpes simplex virus to other antiviral drugs.
Three acyclovir (ACV)-resistant mutants derived from a strain of herpes simplex virus (HSV) type 1 were studied to determine the range of their resistance to nine drugs active against HSV. Two of the mutants were thymidine kinase-deficient (TK-) and were resistant to drugs that are usually phosphorylated by HSV TK. The other mutant induced normal levels of TK; it was of special interest since TK+ viruses appear more likely to multiply well in vivo. This mutant was inhibited by "TK-mediated" drugs: idoxuridine, which is already in use, and two drugs with promising clinical potential, 1-beta-arabinofuranosylthymine and E-5-(2-bromovinyl)-2'-deoxyuridine. All of the mutants were sensitive to trifluorothymidine and 9-beta-D-arabinofuranosyladenine. These results suggest that the study of cross-resistance of HSV strains in vitro will aid in the investigation of alternative drugs for use in effective chemotherapy.
D000212:Acyclovir; D000998:Antiviral Agents / Q000494:pharmacology*; D001087:Arabinonucleosides / Q000494:pharmacology; D001973:Bromodeoxyuridine / Q000031:analogs & derivatives / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D017245:Foscarnet; D006147:Guanine / Q000031:analogs & derivatives / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009154:Mutation; D010746:Phosphonoacetic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D018139:Simplexvirus / Q000187:drug effects* / Q000235:genetics; D013936:Thymidine / Q000031:analogs & derivatives / Q000494:pharmacology; D014271:Trifluridine / Q000494:pharmacology; D014740:Vidarabine / Q000494:pharmacology
D000998:Antiviral Agents; D001087:Arabinonucleosides; C020235:brivudine; D017245:Foscarnet; D006147:Guanine; D014740:Vidarabine; D001973:Bromodeoxyuridine; D010746:Phosphonoacetic Acid; C010032:thymine arabinoside; D014271:Trifluridine; D013936:Thymidine; D000212:Acyclovir