Structure activity relationship of dendrimer microbicides with dual action antiviral activity

具有双重抗病毒活性的树枝状杀微生物剂的构效关系

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作者:David Tyssen, Scott A Henderson, Adam Johnson, Jasminka Sterjovski, Katie Moore, Jennifer La, Mark Zanin, Secondo Sonza, Peter Karellas, Michael P Giannis, Guy Krippner, Steve Wesselingh, Tom McCarthy, Paul R Gorry, Paul A Ramsland, Richard Cone, Jeremy R A Paull, Gareth R Lewis, Gilda Tachedjian

Background

Topical microbicides, used by women to prevent the transmission of HIV and other sexually transmitted infections are urgently required. Dendrimers are highly branched nanoparticles being developed as microbicides. However, the anti-HIV and HSV structure-activity relationship of dendrimers comprising benzyhydryl amide cores and lysine branches, and a comprehensive analysis of their broad-spectrum anti-HIV activity and mechanism of action have not been published.

Conclusions

Dendrimers can be engineered with optimized potency against HIV and HSV representing a unique platform for the controlled synthesis of chemically defined multivalent agents as viral entry inhibitors. SPL7013 is formulated as VivaGel(R) and is currently in clinical development to provide protection against HIV and HSV. SPL7013 could also be combined with other microbicides.

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