Multiple capsid-stabilizing interactions revealed in a high-resolution structure of an emerging picornavirus causing neonatal sepsis

• DOI: 10.1038/ncomms11387
• Publication Date: 2016-07-20T10:04:50Z
• Authors: Shabih Shakeel; Brenda M. Westerhuis; Ausra Domanska; Roman I. Koning; Rishi Matadeen; Abraham J. Koster; Arjen Q. Bakker; Tim Beaumont; Katja C. Wolthers; Sarah J. Butcher
• Keywords: Picornavirus

Abstract The poorly studied picornavirus, human parechovirus 3 (HPeV3) causes neonatal sepsis with no therapies available. Our 4.3-Å resolution structure of HPeV3 on its own and at 15 Å in complex monoclonal antibody Fabs demonstrates the expected picornavirus capsid three distinct features. First, 25% RNA genome 60 sites is highly ordered as confirmed by asymmetric reconstruction, interacts conserved regions proteins VP1 VP3. Second, VP0 N terminus stabilizes inner surface, contrast to other picornaviruses where expulsion VP4, it forms an translocation channel. Last, VP1’s hydrophobic pocket, binding site for antipicornaviral drug, pleconaril, blocked thus inappropriate antiviral development. Together, these results suggest a direction development neutralizing antibodies, drugs based targeting RNA–protein interactions dissection virus assembly basis nucleation.