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Triterpene saponins are a major group of active components in natural products with nonspecific antiviral activities; while T20 peptide(enfuvirtide),which contains a helix zone-binding domain(HBD),is a gp41-specific HIV-1 fusion inhibitor[1-2].In this paper,we report the design,synthesis,and structure-activity relationship(SAR)of a group of hybrid molecules in which bioactive triterpene sapogenins were covalently attached to the HBD-containing peptides via click chemistry.