Structural basis for cross-alphaherpesvirus neutralization by an antibody targeting a conserved hotspot on glycoprotein B.

C12A6 antibody cross-neutralizes HSV-1, HSV-2, and PRV by targeting a conserved epitope on glycoprotein B's Domain I, providing substantial but incomplete protection.

• Why it matters: Broad-spectrum interventions against alphaherpesviruses are lacking, and understanding conserved viral structures is crucial for developing effective therapies to combat diverse infections.
• What they did: Researchers used cryo-electron microscopy to determine structures of C12A6 bound to PRV gB and HSV-2 gB, revealing engagement with a conserved conformational epitope supported by invariant polar contacts and a hydrophobic core.
• The result: Findings clarify the structural basis for cross-neutralization, highlighting the functional architecture of gB Domain I as a promising target for broad-spectrum antiviral development.