title: Feglymycin, a unique natural bacterial antibiotic peptide, inhibits HIV entry by targeting the viral envelope protein gp120.
abstract: Feglymycin (FGM), a natural Streptomyces-derived 13mer peptide, consistently inhibits HIV replication in the lower μM range. FGM also inhibits HIV cell-to-cell transfer between HIV-infected T cells and uninfected CD4(+) T cells and the DC-SIGN-mediated viral transfer to CD4(+) T cells. FGM potently interacts with gp120 (X4 and R5) as determined by SPR analysis and shown to act as a gp120/CD4 binding inhibitor. Alanine-scan analysis showed an important role for l-aspartic acid at position 13 for its anti-HIV activity. In vitro generated FGM-resistant HIV-1 IIIB virus (HIV-1 IIIB(FGMres)) showed two unique mutations in gp120 at positions I153L and K457I. HIV-1 IIIB(FGMres) virus was equally susceptible to other viral binding/adsorption inhibitors with the exception of dextran sulfate (9-fold resistance) and cyclotriazadisulfonamide (>15-fold), two well-described compounds that interfere with HIV entry. In conclusion, FGM is a unique prototype lead peptide with potential for further development of more potent anti-HIV derivatives.
authors.affiliation: Rega Institute for Medical Research, University of Leuven, Leuven, Belgium. geoffrey.ferir@rega.kuleuven.be
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Férir
authors.forename: Anne
authors.initials: A
authors.lastname: Hänchen
authors.forename: Katrien O
authors.initials: KO
authors.lastname: François
authors.forename: Bart
authors.initials: B
authors.lastname: Hoorelbeke
authors.forename: Dana
authors.initials: D
authors.lastname: Huskens
authors.forename: Frank
authors.initials: F
authors.lastname: Dettner
authors.forename: Roderich D
authors.initials: RD
authors.lastname: Süssmuth
authors.forename: Dominique
authors.initials: D
authors.lastname: Schols
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000737:chemistry / Q000494:pharmacology; D015704:CD4 Antigens / Q000187:drug effects; D002460:Cell Line; D055808:Drug Discovery; D015726:Giant Cells / Q000187:drug effects; D015699:HIV Envelope Protein gp120 / Q000037:antagonists & inhibitors*; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000472:pathogenicity / Q000502:physiology; D006801:Humans; D010455:Peptides; D011506:Proteins / Q000737:chemistry / Q000494:pharmacology*; D053586:Virus Internalization / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D019380:Anti-HIV Agents; D001426:Bacterial Proteins; D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D010455:Peptides; D011506:Proteins; C120179:feglymycin; C514793:gp120 protein, Human immunodeficiency virus 1