This revised two year grant has removed all foreign components including animal work to become a fully domestic project focusing on Marburg virus GP protein engineering and crystallization alone and in complex with antibodies already in existence. This grant will result in the necessary templates for vaccine and drug design against Marburg virus through GP. Deliverables will include crystals and atomic coordinates, as well as high yield expression constructs of Marburg virus GP and initial mapping of antibody epitopes on it. We have recently determined crystal structures of both Zaire and Sudan ebolavirus GP, which identify vulnerable, previously untargeted epitopes on the filoviral surface. Optimism for success stems form numerous monoclonal antibodies against MARV already available and our successful crystal structures of two other trimeric, filovirus GPs, each in complex with a different mAb. PHS 398/2590 (Rev. 11/07) Page 1 Continuation Format Page
No antibodies against MARV are yet available for human use. This is the first structure-directed effort to evaluate antibodies against Marburg GP for future therapeutic development. PHS 398/2590 (Rev. 11/07) Page 3 Continuation Format Page
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