Effect of Cytosine Arabinoside,lododeoxyuridine,Ethyldeoxyuridine,Thiocyanatodeoxyuridine,and Ribavirin on Tail Lesion Formation in Mice Infected with Vaccinia Virus

Abstract

Summary

Mice infected intravenously with vaccinia virus develop characteristic lesions over the entire tail surface. This experimental virus infection presents a highly sensitive and reliable model for evaluating the antivaccinia activity of antiviral compounds. Ara-C (1 -β-D-arabinofuranosylcytosine), ribavirin (1-β-D-ribofuranosyl-1,2,4-tria-zole-3-carboxamide), IUdR (5-iodo-2′-deoxyuridine) as well as two novel analogs of IUdR, EtUdR (5-ethyl-2′-deoxyuridine), and NCSUdR (5-thiocyanato-2′-deoxyuri-dine), were found to inhibit the formation of vaccinia tail lesions, when administered in-traperitoneally once daily for 7 days starting immediately after virus infection. The order of (decreasing) activity was: ara-C > IUdR > NCSUdR > ribavirin > EtUdR. Various drug combinations, involving IUdR + ara-C, NCSUdR + ara-C, NCSUdR + IUdR, NCSUdR + ribavirin, etc., were evaluated, but none proved more efficacious than either compound administered alone.

This investigation was supported by grants from the F.G.W.O. (Fonds voor Geneeskundig Wetenschappel-ijk Onderzoek) and the K.U.L. (Katholieke Universi-teit Leuven) “Fonds Derde Cyclus.” M. L. was supported by a postdoctoral fellowship of the K.U.L. “Fonds Derde Cyclus.” We thank Dr. H. A. Jolley (Cyanamid International Co., Pearl River, New York) and Dr. F. Dehaen (Cyanamid Benelux, Lederle Laboratories Division, Brussels) for the generous supply of ribavirin.