Decoy influenza therapies

摘要

The present invention provides umbrella-topology glycan decoys. The present invention provides systems and methods treating influenza infection utilizing inventive umbrella-topology glycan decoys. The present invention provides methods for identifying novel umbrella-topology glycan decoys.

主权项

1. A method for identifying agents useful in the treatment of influenza infection, the method comprising steps of:
(a) providing an influenza hemagglutinin (HA), wherein the HA is characterized in that it preferentially binds to umbrella-topology glycans over cone-topology glycans such that it interacts with HA receptor glycans preferentially found in the human upper respiratory tract; (b) providing a collection of candidate umbrella-topology decoys, which candidate umbrella-topology decoys comprise glycan moieties that share an oligosaccharide branch length characteristic with at least one umbrella-topology glycan selected from the group consisting of:
(i) those depicted in FIG. 6,(ii) those depicted in FIG. 7,(iii) those depicted in FIG. 9,(iv) α2-6 sialylated glycans with length of at least a tetrasaccharide and characterized by one or more of θ<100°, φ angle of Neu5Acα2-6Gal linkage of around −60, and multiple lactosamine units, and(v) combinations thereof; (c) contacting the influenza HA with one or more candidate umbrella-topology decoy from the collection; (d) determining that at least one of the candidate umbrella-topology decoys from the collection competes the binding interaction between the influenza HA and one or more of the HA receptor glycans preferentially found on human upper respiratory tract, so that the candidate umbrella-topology decoy is useful in the treatment of influenza infection.