Structural Superimposition

Abstact

Human astrovirus (HAstV) is a major cause of viral enteritis in children and the older adults worldwide. The eight serotypes of classical HAstVs (HAstV1-8), employ the neonatal Fc receptor (FcRn) as an entry receptor. To elucidate the receptor binding mechanism of HAstVs, we determined the crystal structure of the HAstV8 spike protein complexed with human FcRn. The structure reveals that the HAstV8 spike protein engaged FcRn via a conserved surface depression, which is also present across the other seven classical HAstVs serotypes. The binding interface of HAstV8 spike protein on FcRn largely overlaps with the footprints of three clinically approved FcRn blockers to treat an autoimmune disease. Accordingly, these FcRn inhibitors potently suppress astrovirus infection, significantly reducing viral RNA levels in astrovirus permissive Caco2 cells. Therefore, our study reports a conserved receptor recognition mechanism among human astroviruses and suggests the potential of repurposing clinically approved therapeutics to treat astrovirus infection.