title: 2'-C-methylcytidine as a potent and selective inhibitor of the replication of foot-and-mouth disease virus.
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.
authors.affiliation: Department of Virology, Epizootic Diseases Section, Veterinary and Agrochemical Research Centre, Groeselenberg 99, 1180 Brussels, Belgium. negor@var.fgov.be
authors.forename: Nesya
authors.initials: N
authors.lastname: Goris
authors.forename: Armando
authors.initials: A
authors.lastname: De Palma
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Toussaint
authors.forename: Ina
authors.initials: I
authors.lastname: Musch
authors.forename: Johan
authors.initials: J
authors.lastname: Neyts
authors.forename: Kris
authors.initials: K
authors.lastname: De Clercq
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D006224:Cricetinae; D003562:Cytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D029822:Enterovirus B, Human / Q000187:drug effects / Q000235:genetics; D005536:Foot-and-Mouth Disease / Q000188:drug therapy* / Q000821:virology; D029544:Foot-and-Mouth Disease Virus / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D012367:RNA, Viral / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013552:Swine; D013555:Swine Vesicular Disease / Q000821:virology; D014779:Virus Replication / Q000187:drug effects / Q000235:genetics / Q000502:physiology
chemical_list: D000998:Antiviral Agents; D012367:RNA, Viral; C513402:2'-C-methylcytidine; D003562:Cytidine