Structural engineering of the carbohydrate-binding antiviral entry inhibitor Scytovirin

Scytovirin is a novel potent carbohydrate binding protein with antiviral activity for the HIV-1 virus. It has two binding domains that are homologous with only three residue differences and three aromatics in each domain. Scytovirin's structure and carbohydrate binding interface have been solved and the two domains have different binding affinity. The Scytovirin residues involved in carbohydrate binding were targeted for structural engineering for the purpose of improving binding affinity and understanding the specificity for the HIV-1 virus. Mutations were strategically made in the protein: in the aromatic residues and in the three residues that are naturally different between the two domains. The alteration of some of these residues proved to increase the carbohydrate binding affinity, as well as improve NMR spectral resolution.