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Griffithsin, a potent HIV entry inhibitor, is an excellent candidate for anti‐HIV microbicide
Author(s) -
Emau P.,
Tian B.,
O’keefe B.R.,
Mori T.,
McMahon J.B.,
Palmer K.E.,
Jiang Y.,
Bekele G.,
Tsai C.C.
Publication year - 2007
Publication title -
journal of medical primatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.31
H-Index - 42
eISSN - 1600-0684
pISSN - 0047-2565
DOI - 10.1111/j.1600-0684.2007.00242.x
Subject(s) - microbicide , human immunodeficiency virus (hiv) , microbicides for sexually transmitted diseases , vaginal microbicide , virology , entry inhibitor , pharmacology , medicine , virus , viral entry , health services , viral replication , population , environmental health
Background The predominant mode of HIV‐1 transmission is by heterosexual contact. The cervical/vaginal mucosa is the main port of HIV entry in women. A safe and effective topical microbicide against HIV is urgently needed to prevent sexual transmission. Hence, we evaluated griffithsin (GRFT), a 12.7 kDa carbohydrate‐binding protein, both native and recombinant GRFT, potently inhibited both CXCR4‐and CCR5‐tropic HIV infection and transmission in vitro . Methods The antiviral efficacy of native and recombinant GRFT against CXCR4‐and CCR5‐tropic HIV and SHIV strains and SIVmac251 was evaluated by in vitro assays. We also evaluated the time course of antiviral activity and stability of GRFT in cervical/vaginal lavage as a function of pH 4–8. Results Griffithsin blocked CXCR4‐and CCR5‐tropic viruses at less than 1 n m concentrations and exhibited a high potency. GRFT was stable in cervical/vaginal lavage fluid and maintained a similar potency of anti‐HIV activity. GRFT is not only a highly potent HIV entry inhibitor, but also prevents cell fusion and cell‐to‐cell transmission of HIV. Conclusions The in vitro efficacy of GRFT revealed low cytotoxicity, high potency, rapid onset of antiviral activity and long‐term stability in cervical/vaginal lavage. GRFT is an excellent candidate for anti‐HIV microbicide development.