2'-C-methylcytidine as a potent and selective inhibitor of the replication of foot-and-mouth disease virus |
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Authors: | Goris Nesya De Palma Armando Toussaint Jean-François Musch Ina Neyts Johan De Clercq Kris |
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Affiliation: | Department of Virology, Epizootic Diseases Section, Veterinary and Agrochemical Research Centre, Groeselenberg 99, 1180 Brussels, Belgium. negor@var.fgov.be |
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Abstract: | We report on the potent and selective in vitro antiviral activity of 2'-C-methylcytidine (2'-C-MetCyt) against foot-and-mouth disease virus (FMDV). FMDV belongs to the Picornaviridae and has the potential to cause devastating epidemics in livestock. The 50% and 90% effective concentrations (EC50 and EC90) for inhibition of the FMDV-induced cytopathic effect (CPE) formation were 6.4+/-3.8 and 10.8+/-5.4 microM. Comparable EC50 values for inhibition of viral RNA synthesis were observed. Treatment of FMDV-infected BHK-21 cells with 77 microM 2'-C-MetCyt resulted in a (1.6-3.2)x10(3)-fold reduction of infectious virus yield. Time-of-drug addition experiments suggest that 2'-C-MetCyt interacts with viral replication at a time point that coincides with the onset of intracellular viral RNA synthesis. In contrast to emergency vaccination, a potent and selective antiviral agent may provide almost immediate (prophylactic/therapeutic) protection against infection and thus constitute an important alternative/supplementary option to contain outbreaks such as those caused by FMDV. |
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