Computational Design of Trimeric Influenza-Neutralizing Proteins Targeting the Hemagglutinin Receptor Binding Site

Strauch EM, et al., 35(7):667-671, Nat Biotechnol., 2017

Hemagglutinin (HA) is a glycoprotein found on the surface of the influenza viruses that enable viral entry into host cells. Binding sites on HA are highly conserved and they present excellent targets for lead design. Reported herein is a computational design of high-avidity trimeric influenza-neutralizing proteins targeting the HA receptor binding site of influenza A. The binding affinity of H3 HK68 HA towards monomeric HSB.2 and trimeric HSB.2 was studied by using Bio-layer Interferometry (BLI). A Pall ForteBio Octet RED96 instrument equipped with Streptavidin (SA) Biosensor probes were used to perform binding assays. Biotinylated HA was immobilized onto SA sensor tips. BLI data were fitted using a 1:1 binding model. KD values were determined. Authors suggest that the designed trimeric proteins have important implications toward diagnostic and therapeutic applications.

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