Mechanisms and Modifications of Naturally Occurring Host Defense Peptides for Anti-HIV Microbicide Development

    Authors

    C. R. Eade; M. P. Wood;A. M. Cole

    Comments

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    Abbreviated Journal Title

    Curr. HIV Res.

    Keywords

    Defensin; HIV transmission; host defense peptides; microbicide; development; modification of peptides; HUMAN-IMMUNODEFICIENCY-VIRUS; INHIBITORY MACROCYCLIC PEPTIDES; CHEMOKINE; RECEPTOR CXCR4; ANTIMICROBIAL PEPTIDES; IN-VITRO; THETA-DEFENSINS; ALPHA-DEFENSINS; PHARMACOPHORE IDENTIFICATION; TYPE-1 INFECTION; ENTRY; INHIBITOR; Immunology; Infectious Diseases; Virology

    Abstract

    Despite advances in the treatment of HIV infection, heterosexual transmission of HIV remains high, and vaccines to prevent HIV acquisition have been unfruitful. Vaginal microbicides, on the other hand, have demonstrated considerable potential for HIV prevention, and a variety of compounds have been screened for their activity and safety as anti-HIV microbicides. Among these are the naturally occurring host defense peptides, small peptides from diverse lineages with intrinsic antiviral activity. Naturally occurring host defense peptides with anti-HIV activity are promising candidates for vaginal microbicide development. Their structural variance and accompanying mechanistic diversity provide a wide range of inhibitors whose antiviral activity can be exerted at nearly every stage of the HIV lifecycle. Additionally, peptide modification has been explored as a method for improving the anti-HIV activity of host defense peptides. Structure-and sequence-based alterations have achieved varying success in improving the potency and specificity of anti-HIV peptides. Overall, peptides have been discovered or engineered to inhibit HIV with therapeutic indices of > 1000, encouraging their advancement toward clinical trials. Here we review the naturally occurring anti-HIV host defense peptides, demonstrating their breadth of mechanistic diversity, and exploring approaches to enhance and optimize their activity in order to expedite their development as safe and effective anti-HIV vaginal microbicides.

    Journal Title

    Current Hiv Research

    Volume

    10

    Issue/Number

    1

    Publication Date

    1-1-2012

    Document Type

    Article

    Language

    English

    First Page

    61

    Last Page

    72

    WOS Identifier

    WOS:000300409000009

    ISSN

    1570-162X

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