Inhibitory effects of ribavirin alone or combined with human alpha interferon on feline infectious peritonitis virus replication in vitro.

作者: Richard C. Weiss , Theresia Oostrom-Ram

DOI: 10.1016/0378-1135(89)90049-7

关键词: RibavirinIn vitroIn vivoInfectivityCytotoxic T cellInterferonVirologyTherapeutic indexAlpha interferonBiology

摘要: Abstract The antiviral activities of ribavirin (1-β- D -ribofuranosyl-1,2,4-triazole-3-carboxamide; virazole), either alone or in combination with recombinant human leukocyte (alpha) interferon (rHuIFN-α), were evaluated against feline infectious peritonitis virus (FIPV) kidney-cell cultures. 50% inhibitory dose (ID 50 ) for uninfected, rapidly dividing cells was ∼17 μ g ml −1 whereas the ID FIPV 2.5 . therapeutic index (TI) (i.e. ratio minimum cell-toxic to virus-inhibitory dose) 6.8. Although a dose-dependent inhibition viral infectivity occurred at non-toxic doses, maximum effects (⩾4 log 10 reduction FIPV) cytotoxic doses. When low moderate doses combined 100 U rHuIFN-α , resulting significantly greater than sum observed from alone. Significant synergistic interactions 1, 5, 12.5 and 25 Synergistic combinations produced up an 80-fold 200-fold relative increase compared that by equivalent respectively, In cell growth studies, addition test did not anticellular effect alone; seemingly, potentiation activity independent any additive effects. Potentially, two agents vivo may decrease required thus reduce drug toxicity.

参考文章(15)
Stephen A. Spector, Michael Tyndall, Eileen Kelley, Effects of acyclovir combined with other antiviral agents on human cytomegalovirus The American Journal of Medicine. ,vol. 73, pp. 36- 39 ,(1982) , 10.1016/0002-9343(82)90060-2
Yvonne J. Bryson, Promising new antiviral drugs Journal of The American Academy of Dermatology. ,vol. 18, pp. 212- 218 ,(1988) , 10.1016/S0190-9622(88)70031-6
R Dolin, Antiviral chemotherapy and chemoprophylaxis. Science. ,vol. 227, pp. 1296- 1303 ,(1985) , 10.1126/SCIENCE.2983421
T. L. Stanwick, R. F. Schinazi, D. E. Campbell, A. J. Nahmias, Combined Antiviral Effect of Interferon and Acyclovir on Herpes Simplex Virus Types 1 and 2 Antimicrobial Agents and Chemotherapy. ,vol. 19, pp. 672- 674 ,(1981) , 10.1128/AAC.19.4.672
A. Billiau, H. Sobis, P. De Somer, Influence of interferon on virus particle formation in different oncornavirus carrier cell lines International Journal of Cancer. ,vol. 12, pp. 646- 653 ,(1973) , 10.1002/IJC.2910120313
L.J. REED, H. MUENCH, A SIMPLE METHOD OF ESTIMATING FIFTY PER CENT ENDPOINTS American Journal of Epidemiology. ,vol. 27, pp. 493- 497 ,(1938) , 10.1093/OXFORDJOURNALS.AJE.A118408
F Valeriote, H s Lin, Synergistic interaction of anticancer agents: a cellular perspective. Cancer chemotherapy reports. ,vol. 59, pp. 895- 900 ,(1975)
R. A. Crandell, E. W. Despeaux, Cytopathology of feline viral rhinotracheitis virus in tissue cultures of feline renal cells. Experimental Biology and Medicine. ,vol. 101, pp. 494- 497 ,(1959) , 10.3181/00379727-101-24993