Fejerlectin, a Lectin-like Peptide from the Skin of Fejervarya limnocharis, Inhibits HIV-1 Entry by Targeting Gp41

[Image: see text] Human immunodeficiency virus type 1 (HIV-1) is mainly transmitted by sexual intercourse, and effective microbicides preventing HIV-1 transmission are still required. Amphibian skin is a rich source of defense peptides with antiviral activity. Here, we characterized a lectin-like peptide, fejerlectin (RLCYMVLPCP), isolated from the skin of the frog Fejervarya limnocharis. Fejerlectin showed significant hemagglutination and d-(+)-galacturonic acid-binding activities. Furthermore, fejerlectin suppressed the early entry of HIV-1 into target cells by binding to the N-terminal heptad repeat of HIV-1 gp41 and preventing 6-HB formation and Env-mediated membrane fusion. Fejerlectin is the smallest lectin-like peptide identified to date and represents a new and promising platform for anti-HIV-1 drug development.