Nucleoside derivatives having a benzodithiol-2-yl (BDT) group were synthesized and examined for their anti-bovine viral diarrhea virus (BVDV) activities. Other substituents structurally similar to the BDT group such as 1,3-benzodioxol-2-yl, benzimidazol-2-yl and 1-oxo-benzodithiol-2-yl groups were not effective as the pharmacophore. The anti-BVDV assay revealed that 2'-O-BDT-guanosine and 2'-O-BDT-inosine had the strongest anti-BVDV activity among the nucleoside derivatives synthesized in this study. Since BVDV has been recognized as a surrogate for human hepatitis C virus (HCV), the BDT-modified nucleosides might become a new class of lead compounds to find nucleoside-type anti-HCV agents such as ribavirin.