Key result
2'-O-BDT-guanosine and 2'-O-BDT-inosine demonstrate strong anti-BVDV activity, suggesting potential as lead anti-HCV agents.
BDT-modified nucleosides show promise as lead compounds for developing new anti-HCV agents based on their anti-BVDV activity.
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BDT-modified nucleosides merit further preclinical testing as anti-HCV leads; animal data leave open human efficacy and safety.
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.
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Seio et al. (2004) studied Bovine viral diarrhea virus (BVDV) infection. Benzodithiol-2-yl (BDT)-substituted nucleoside derivatives (e.g., 2'-O-BDT-guanosine and 2'-O-BDT-inosine) vs. Nucleoside derivatives with other substituents (e.g., 1,3-benzodioxol-2-yl, benzimidazol-2-yl) was evaluated on Anti-BVDV activity. 2'-O-BDT-guanosine and 2'-O-BDT-inosine demonstrated the strongest anti-BVDV activity among the synthesized nucleoside derivatives, suggesting potential as lead compounds for anti-HCV agents.
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