బయోకెమిస్ట్రీ & ఫిజియాలజీ: ఓపెన్ యాక్సెస్

నైరూప్య

Scytovirin Engineering Improves Carbohydrate Affinity and HIV-1 Entry Inhibition

Hana McFeeters, Morgan J. Gilbert, Alexandra M. Wood, Charity B. Haggenmaker, Jennifer Jones, Olaf Kutsch and Robert L. McFeeters

Scytovirin, a cyanobacterium derived carbohydrate binding protein, acts as a potent HIV-1 entry inhibitor and could hold promise as a potential topical microbicide. Viral specificity is achieved as Scytovirin recognizes carbohydrate moieties rarely found in the extracellular matrix, but which are abundant on viral proteins. With the goal to improve the anti-viral capacity of Scytovirin, we here analyze the factors contributing to the Scytovirin anti-viral effect. We show that aromatic substitutions in the lower affinity C-terminal domain of Scytovirin lead to tighter carbohydrate binding. Several other mutations or an addition to the N-terminal abolish carbohydrate binding and abrogate the antiviral effect. Moreover, the increased binding affinity translates directly to improved antiviral efficacy. These studies improve our understanding of the Scytovirin:carbohydrate interaction and provide a blueprint for additional targeted mutations to advance Scytovirin as an entry inhibitor.