Inhibition of Phlebovirus Infections in vivo by Tiazofurin and Selenazofurin

Abstract

The c-nucleosides tiazofurin and selenazofurin were evaluated in mice against the Adames strain of Punta Toro virus, a Phlebovirus related to Rift Valley fever and sandfly fever viruses. When administered subcutaneously (s.c.) twice a day for 5 days starting 4h before virus inoculation, tiazofurin reduced mortality, hepatic icterus scores, serum aspartate aminotransferase (AST) levels, and serum virus titres at 250–500 mg kg−1 day−1. Liver virus titres were not reduced in these treated animals, however. Oral tiazofurin treatment was effective by the same criteria at 375 and 750 mg kg−1, except that liver virus titres were reduced at 750 mg kg−1. Similar effects were observed with selenazofurin given s.c. (80–160 mg kg−1) or orally (80–320 mg kg−1) for 5 days. Selenazofurin suppressed liver virus titres by oral but not s.c. treatment. In a time-course study tiazofurin was effective s.c. at 250–1000 mg kg−1 when administered once only at 48 h after virus inoculation, whereas treatments at 4, 24, 72 and 96 h were less or not effective. By comparison with published results, tiazofurin and selenazofurin do not appear to be as active or selective as ribavirin and ribamidine against Punta Toro virus infections in mice.