Feglymycin, a unique natural bacterial antibiotic peptide, inhibits HIV entry by targeting the viral envelope protein gp120

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• 作者：Geoffrey F¨¦rir ; Anne H?nchen ; Katrien O. Fran?ois ; Bart Hoorelbeke ; Dana Huskens ; Frank Dettner ; Roderich D. S¨¹ssmuth ; Dominique Schols
• 关键词：AIDS ; Acquired immune deficiency syndrome ; ARV ; Antiretroviral ; CADA ; Cyclotriazadisulfonamide ; CBA(s) ; Carbohydrate-binding agent(s) ; CPE ; Cytopathic effect ; DCs ; Dendritic cells ; DC-SIGN ; Dendritic cell-specific ICAM-3 grabbing non-integrin ; DS5000/8000
• 刊名：Virology
• 出版年：2012
• 出版时间：25 November, 2012
• 年：2012
• 卷：433
• 期：2
• 页码：308-319
• 全文大小：1397 K

文摘

Feglymycin (FGM), a natural Streptomyces-derived 13mer peptide, consistently inhibits HIV replication in the lower ¦ÌM 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.