Structural Biology of an Antiviral Entry Inhibitor

Division Of Basic Sciences - Nci

Investigators

Abstract

In collaboration with the MTDP, we reported the solution structure of the novel anti-viral protein Scytovirin, published in the Journal of Molecular Biology (2007). Our studies included examination of the oligosaccharide binding, which is the key element of the entry-inhibition mechanism proposed for Scytovirin. This protein exhibits remarkable anti-viral activity against HIV and Ebola. Animal studies indicated a promising agent. We are continuing to study the details of the oligosaccharide binding. Through the use of structure-based, site-directed engineering, we have generated altered carbohydrate binding affinity and are using this characteristic to pursue potential therapeutic variants of the native protein. We are also pursuing mutants and chimeras with reduced binding to provide tools with which to dissect the interaction with viral gp41 and gp120. This project will be phased out in FY2010.