Proc Natl Acad Sci U S A. 2011 Aug 23; 108(34):14079-84.

PubMed ID: 21799112

Designed oligomers of cyanovirin-N show enhanced HIV neutralization

Keeffe JR, Gnanapragasam PN, Gillespie SK, Yong J, Bjorkman PJ, Mayo SL

Cyanovirin-N (CV-N) is a small, cyanobacterial lectin that neutralizes many enveloped viruses, including human immunodeficiency virus type I (HIV-1). This antiviral activity is attributed to two homologous carbohydrate binding sites that specifically bind high mannose glycosylation present on envelope glycoproteins such as HIV-1 gp120. We created obligate CV-N oligomers to determine whether increasing the number of binding sites has an effect on viral neutralization. A tandem repeat of two CV-N molecules (CVN(2)) increased HIV-1 neutralization activity by up to 18-fold compared to wild-type CV-N. In addition, the CVN(2) variants showed extensive cross-clade reactivity and were often more potent than broadly neutralizing anti-HIV antibodies. The improvement in activity and broad cross-strain HIV neutralization exhibited by these molecules holds promise for the future therapeutic utility of these and other engineered CV-N variants.