Efficacy of 2′-C-methylcytidine against yellow fever virus in cell culture and in a hamster model

Yellow fever virus (YFV) continues to cause outbreaks of disease in endemic areas where vaccine is underutilized. Due to the effectiveness of the vaccine, antiviral development solely for the treatment of YFV is not feasible, but antivirals that are effective in the treatment of related viral diseases may be characterized for potential use against YFV as a secondary indication disease. 2′-C-methylcytidine (2′-C-MeC), a compound active against hepatitis C virus, was found to have activity against the 17D vaccine strain of YFV in cell culture (EC90 = 0.32 μg/ml, SI = 141). This compound was effective when added as late as 16 h after virus challenge of Vero cells. When administered to YFV-infected hamsters 4 h prior to virus challenge at a dose as low as 80 mg/kg/d, 2′-C-MeC was effective in significantly improving survival and other disease parameters (weight change, serum ALT, and liver virus titers). Disease was improved when compound was administered beginning as late as 3 d post-virus infection. Broadly active antiviral compounds, such as 2′-C-MeC, represent potential for the development of compounds active against related viruses for the treatment of YFV.