Cryo-EM Reveals How Andes Hantavirus Binds Human Cell Receptor

Andes hantavirus uses its surface spike protein to bind PCDH1, a receptor on human cells, as part of infection. In a study published in Nature, researchers from Albert Einstein College of Medicine, Institut Pasteur and LSU Health Shreveport used cryo-electron microscopy to determine how the virus spike interacts with PCDH1. They used an engineered scaffold to stabilize the spike for structural analysis.

The structures showed that one PCDH1 molecule binds in a deep pocket at the center of the virus’s square-shaped spike. The team also examined antibodies from people with hantavirus infection that had previously been shown to block the receptor interaction. Some bound near the pocket’s entrance and prevented PCDH1 binding, but did not extend as deeply into the pocket as the receptor. The researchers said viral changes that limit antibody access may leave receptor binding intact.

The work provides a structural explanation for receptor recognition and points to the pocket as a possible target for antiviral development, including approaches designed to reach deeper than antibodies. The researchers suggested this could inform strategies against Andes virus and Sin Nombre virus. However, the study reports structural findings, not a tested treatment or evidence of clinical benefit; therapeutic approaches remain at an early development stage.