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l -Chicoric acid is an inhibitor of human immunodeficiency virus type 1 (HIV-1) integrase in vitro and of HIV-1 replication in tissue culture. Following 3 months of selection in the presence of increasing concentrations ofl -chicoric acid, HIV-1 was completely resistant to the compound. Introduction of the mutant integrase containing a single glycine-to-serine amino acid change at position 140 into the native,l -chicoric acid-sensitive virus demonstrated that this change was sufficient to confer resistance tol -chicoric acid. These results confirm through natural selection previous biochemical studies showing thatl -chicoric acid inhibits integrase and that the drug is likely to interact at residues near the catalytic triad in the integrase active site.

journal of virology

Resistance to the Anti-Human Immunodeficiency Virus Type 1 Compound <scp>l</scp> -Chicoric Acid Results from a Single Mutation at Amino Acid 140 of Integrase

Resistance to the Anti-Human Immunodeficiency Virus Type 1 Compound l -Chicoric Acid Results from a Single Mutation at Amino Acid 140 of Integrase