The occurrence of highly pathogenic avian influenza virus H5N1 highlights the urgent need for new classes of antiviral drugs. Inhibition of H5N1 entry into cells may be an effective strategy. We report the first three small molecule inhibitors saponins with 3-O-beta-chacotriosyl residue, which showed potent inhibitory activity with IC(50) of 7.22-9.25 microM. The subsequent SAR studies showed the 3-O-beta-chacotriosyl residue was essential for the activity, and the aglycone structure also affected the activity.

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