2--c-methylcytidine has been researched along with Foot-and-Mouth-Disease* in 3 studies
3 other study(ies) available for 2--c-methylcytidine and Foot-and-Mouth-Disease
| Article | Year |
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Proof of concept for the inhibition of foot-and-mouth disease virus replication by the anti-viral drug 2'-C-methylcytidine in severe combined immunodeficient mice.
Recent European contingency plans envisage emergency vaccination as an animal-friendly control strategy for foot-and-mouth disease (FMD). Anti-viral drugs may be used as an alternative or complementary measure. We here demonstrate that the nucleoside analogue 2'-C-methylcytidine (2'CMC) protects severe combined immunodeficient (SCID) mice against lethal FMD virus infection. In brief, SCID mice were inoculated with serotype A FMD virus and treated for five consecutive days with 2'CMC. All 15 treated mice remained healthy until the end of the study at 14 days post-infection (dpi). At that time, viral RNA was no longer detected in 13 of 15 treated mice. All eight untreated mice suffered from an acute generalized disease and were euthanized for ethical reasons on average at 4 dpi. These results illustrate the potential of small molecules to control FMD. Topics: Animals; Antiviral Agents; Cytidine; Disease Models, Animal; Foot-and-Mouth Disease; Foot-and-Mouth Disease Virus; Mice; Mice, SCID; RNA, Viral | 2014 |
In vitro surrogate models to aid in the development of antivirals for the containment of foot-and-mouth disease outbreaks.
Foot-and-mouth disease virus (FMDV) is a highly pathogenic member of the genus Aphthovirus (family Picornaviridae) that is only to be manipulated in high-containment facilities, thus complicating research on and discovery of antiviral strategies against the virus. Bovine rhinitis B virus (BRBV) and equine rhinitis A virus (ERAV), phylogenetically most closely related to FMDV, were explored as surrogates for FMDV in antiviral studies. Although no efficient cell culture system has been reported so far for BRBV, we demonstrate that infection of primary bovine kidney cells resulted in an extensive but rather poorly-reproducible induction of cytopathic effect (CPE). Madin-Darby bovine kidney cells on the other hand supported viral replication in the absence of CPE. Antiviral tests were developed for ERAV in Vero A cells employing a viral RNA-reduction assay and CPE-reduction assay; the latter having a Z' factor of 0.83±0.07. The BRBV and ERAV models were next used to assess the anti-aphthovirus activity of two broad-spectrum antiviral agents 2'-C-methylcytidine (2CMC) and ribavirin, as well as of the enterovirus-specific inhibitor enviroxime. The effects of the three compounds in the CPE-reduction (ERAV) and viral RNA-reduction assays (BRBV and ERAV) were comparable. Akin to 2CMC, compound A, a recently-discovered non-nucleoside pan-serotype FMDV inhibitor, also inhibited the replication of both BRBV and ERAV, whereas enviroxime was devoid of activity. The BRBV and ERAV surrogate models reported here can be manipulated in BSL-2 laboratories and may facilitate studies to unravel the mechanism of action of novel FMDV inhibitors. Topics: Animals; Antiviral Agents; Aphthovirus; Benzimidazoles; Cattle; Cell Line; Chlorocebus aethiops; Cytidine; Cytopathogenic Effect, Viral; Drug Discovery; Foot-and-Mouth Disease; Models, Theoretical; Oximes; Ribavirin; RNA, Viral; Sulfonamides; Virus Cultivation; Virus Replication | 2014 |
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. Topics: Animals; Antiviral Agents; Cricetinae; Cytidine; Enterovirus B, Human; Foot-and-Mouth Disease; Foot-and-Mouth Disease Virus; Reverse Transcriptase Polymerase Chain Reaction; RNA, Viral; Swine; Swine Vesicular Disease; Virus Replication | 2007 |