Nucleoside analogs as potential antiviral agents for dengue virus infections

Dengue virus is the causative agent of dengue fever and also the most prevalent mosquito borne viral pathogen. Up until now, treatments for dengue fever rely mainly on intensive supportive therapies. This study aimed to investigate in vitro antiviral activities of selected nucleoside analogs. These drugs were selected based on their good interactions with dengue virus replicating enzyme in a computer modeling study. The cytotoxicity of the nucleoside analogs in green monkey kidney cell line (VERO) was verified using the MTT [(3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. Among the drugs tested, adenovir dipivoxil exhibited toxicity to cells with only 20–40% cell viability at drug concentrations above 100 µM. Therefore, adenovir dipivoxil was omitted from the plaque reduction assay. The nucleoside analogs were further evaluated in a plaque reduction assay and ribavirin was used as a positive control. VERO cells were infected with dengue virus-2 at a multiplicity of infection of 0.4 and then treated with different concentrations of nucleoside analogs. Virus plaques were observed and counted after 7 days of incubation. The results showed that valganciclovir and stavudine inhibited dengue virus-2 replication by 6–21%. These nucleoside analogs may, therefore, have the potential to be used in treating dengue infections.