In this study we report the synthesis and activity against bovine viral diarrhea virus (BVDV) of a novel series of bicycle δ-sultones containing γ-lactones. BVDV is responsible for major losses in cattle. Some of the synthesized δ-sultones showed pronounced anti-BVDV activity with EC50 values of 0.12-1.0μM and no significant cytotoxicity. Among them, the ortho bromosubstituted derivative 4f (EC50=0.12μM) showed better antiviral activity than other derivatives and was 10 fold more that of than positive control ribavirin (EC50=1.3μM). BVDV is also considered to be a valuable surrogate for the hepatitis C virus (HCV) in antiviral drug studies. The above results provided a novel candidate for the development of anti-HCV agents.