2'-C-methylcytidine as a potent and selective inhibitor of the replication of foot-and-mouth disease virus.
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.
Goris
Nesya
N
Department of Virology, Epizootic Diseases Section, Veterinary and Agrochemical Research Centre, Groeselenberg 99, 1180 Brussels, Belgium. negor@var.fgov.be
De Palma
Armando
A
Toussaint
Jean-François
JF
Musch
Ina
I
Neyts
Johan
J
De Clercq
Kris
K
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
D000998:Antiviral Agents; D012367:RNA, Viral; C513402:2'-C-methylcytidine; D003562:Cytidine