trilobatin and HIV-Infections

HIV-1 transmembrane protein gp41 plays a crucial role by forming a stable six-helix bundle during HIV entry. Due to highly conserved sequence of gp41, the development of an effective and safe small-molecule compound targeting gp41 is a good choice. Currently, natural polyanionic ingredients with anti-HIV activities have aroused concern. Here, we first discovered that a glycosylated dihydrochalcone, trilobatin, exhibited broad anti-HIV-1 activity and low cytotoxicity in vitro. Site-directed mutagenesis analysis suggested that the hydrophobic residue (I564) located in gp41 pocket-forming site is pivotal for anti-HIV activity of trilobatin. Furthermore, trilobatin displayed synergistic anti-HIV activities combined with other antiretroviral agents. Trilobatin has a good potential to be developed as a small-molecule HIV-1 entry inhibitor for clinical combination therapy.

Topics: Animals; Anti-HIV Agents; Cells, Cultured; CHO Cells; Cricetinae; Cricetulus; Drug Evaluation, Preclinical; Flavonoids; HEK293 Cells; HIV Envelope Protein gp41; HIV Infections; HIV-1; Humans; Hydrophobic and Hydrophilic Interactions; Molecular Targeted Therapy; Polyphenols; Virus Internalization