Comparison of the antiviral effects of 5-methoxymethyldeoxyuridine-5'-monophosphate with adenine arabinoside-5'-monophosphate.
Methoxymethyldeoxyuridine-5'-monophosphate (MMUdR-MP) and arabinofuranosyladenine-5'-monophosphate (Ara-AMP) had significant antiviral activity against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in RK-13 and Vero cells. MMUdR-MP and Ara-AMP were more potent than methoxymethyldeoxyuridine (MMUdR) and arabinofuranosyladenine (Ara-A) against the MS strain of HSV-2. MMUdR-MP inhibited replication of HSV-1r (mutant resistant to MMUdR). MMUdR in combination with Ara-AMP showed additive activity; whereas the MMUdR-MP and Ara-AMP combination was antagonistic against herpes viruses. MMUdR in combination with Ara-A was synergistic in reducing the log virus yield. Cytotoxicity (microscopic lesions) was observed on exposure to MMUdR-MP and Ara-AMP at 450 and 90 microM, respectively. Rapidly proliferating RK-13 cells exposed to Ara-AMP (64 microM) were killed. In the same system, the cells surviving after incubation with MMUdR-MP (650 microM), multiplied at an almost normal rate.
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000633:toxicity; D001088:Arabinonucleotides / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D003857:Deoxyuridine / Q000031:analogs & derivatives / Q000494:pharmacology*; D011817:Rabbits; D018139:Simplexvirus / Q000187:drug effects; D013938:Thymidine Monophosphate / Q000031:analogs & derivatives*; D013942:Thymine Nucleotides / Q000494:pharmacology*; D014740:Vidarabine / Q000494:pharmacology; D001084:Vidarabine Phosphate / Q000494:pharmacology*; D010948:Viral Plaque Assay; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D001088:Arabinonucleotides; D013942:Thymine Nucleotides; D001084:Vidarabine Phosphate; D013938:Thymidine Monophosphate; C024722:5-methoxymethyl-2'-deoxyuridine; C039476:5-methoxymethyl-2'-deoxyuridine-5'-monophosphate; D014740:Vidarabine; D003857:Deoxyuridine