| References: |
Beta-d-N4-hydroxycytidine (NHC) is a nucleoside analogue that has antipestivirus and antihepacivirus activities; inhibits the production of cytopathic BVDV RNA with EC90 of 5.4 uM, also has an EC50 of 5 uM for replicon RNA reduction in Huh7 cells; also is a novel inhibitor of CHIKV (Chikungunya virus), inhibits venezuelan equine encephalitis virus (VEEV) with EC50 of <1 uM.The results demonstrate that NHC is a very potent antiviral agent. It affects both the release of genome RNA-containing VEE virions and their infectivity. Both of these antiviral activities are determined by the NHC-induced accumulation of mutations in virus-specific RNAs. The antiviral effect is most prominent when NHC is applied early in the infectious process, during the amplification of negative- and positive-strand RNAs in infected cells. Most importantly, only a low-level resistance of VEEV to NHC can be developed, and it requires acquisition and cooperative function of more than one mutation in nsP4. These adaptive mutations are closely located in the same segment of nsP4. Our data suggest that NHC is more potent than ribavirin as an anti-VEEV agent and likely can be used to treat other alphavirus infections. |
