Affiliation:
1. Department of Microbiology, Western College of Veterinary Medicine, University of Saskatchewan, and Animal Pathology Division, Health of Animals Branch, Agriculture Canada Saskatoon, Saskatchewan S7N 0W0, Canada
Abstract
The antiviral activity of 5-methoxymethyl-2′-deoxyuridine (MMUdR) was compared with that of 5-iodo-2′-deoxyuridine (IUdR), cytosine arabinoside (Ara-C), and adenine arabinoside (Ara-A). At concentrations of 2 to 4 μg/ml, MMUdR was inhibitory to herpes simplex virus type 1, but concentrations as high as 128 μg/ml were not inhibitory to three other herpesviruses tested (equine rhinopneumonitis virus, murine cytomegalovirus, and feline rhinopneumonitis virus) or to vaccinia virus. The other nucleosides, in contrast, were inhibitory at similar concentrations (1 to 8 μg/ml) against all viruses tested. The inhibition of HSV-1 by MMUdR appeared to be the result of interference with virus replication rather than the result of drug toxicity to host cells. The drug was not toxic to host cells at 100 times the antiviral concentrations, and pretreatment of host cells with high concentrations of MMUdR had no effect on subsequent virus replication. Combination of MMUdR with either IUdR, Ara-A, or Ara-C gave an enhanced antiviral effect, suggesting that the mechanism of action of MMUdR is different from that of the other three drugs. Antiviral indexes were calculated for each compound and were found to be >250, 80, 40, and 8 for MMUdR, IUdR, Ara-A, and Ara-C, respectively. These were defined as the minimum dose at which toxicity was observed microscopically divided by the dose which reduced plaque numbers by 50%.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Reference27 articles.
1. Allison A. C. 1972. Immunity against viruses p. 51-53. In I. Gililand and J. Francis (ed.) Scientific basis of medicine: annual reviews. The Althone Press London.
2. Interactions of antibodies, complement components and various cell types in immunity against viruses and pyogenic bacteria;Allison A. C.;Transplant. Rev.,1974
3. Synthesis of 5-substituted ether derivatives of 5-hydroxymethyldeoxyuridine and their a-isomers;Bubbar G. L.;Can. J. Chem.,1970
4. Effect of uracil mustard and several anti-tumor drugs on the primary antibody response in rate and mice;Buskirk H. H.;J. Natl. Cancer Inst.,1965
5. Cell culture studies on antiviral agents. 1. Action of cytosine arabinoside and some comparisons with 5-iodo-2'deoxyuridine;Buthala D. A.;Proc. Soc. Exp. Biol. Med.,1964
Cited by
50 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献