8AYY

Poliovirus type 3 (strain Saukett) stabilised virus-like particle (PV3 SC8) in complex with GSH and Pleconaril

Summary for 8AYY

• Entry DOI: 10.2210/pdb8ayy/pdb
• Related: 8AYX 8AYZ
• EMDB information: 15725 15726 15727
• Descriptor: Capsid protein, VP1, Capsid protein, VP0, Capsid protein, VP3, ... (5 entities in total)
• Functional Keywords: capsid protein, virus like particle, glutathione, inhibitor, complex
• Biological source: Human poliovirus 3; More
• Total number of polymer chains: 3
• Total formula weight: 98189.58

Authors

Bahar, M.W.,Fry, E.E.,Stuart, D.I. (deposition date: 2022-09-04, release date: 2022-12-07, Last modification date: 2024-07-24)

Primary citation

Bahar, M.W.,Nasta, V.,Fox, H.,Sherry, L.,Grehan, K.,Porta, C.,Macadam, A.J.,Stonehouse, N.J.,Rowlands, D.J.,Fry, E.E.,Stuart, D.I.
A conserved glutathione binding site in poliovirus is a target for antivirals and vaccine stabilisation.
Commun Biol, 5:1293-1293, 2022

PubMed Abstract: Strategies to prevent the recurrence of poliovirus (PV) after eradication may utilise non-infectious, recombinant virus-like particle (VLP) vaccines. Despite clear advantages over inactivated or attenuated virus vaccines, instability of VLPs can compromise their immunogenicity. Glutathione (GSH), an important cellular reducing agent, is a crucial co-factor for the morphogenesis of enteroviruses, including PV. We report cryo-EM structures of GSH bound to PV serotype 3 VLPs showing that it can enhance particle stability. GSH binds the positively charged pocket at the interprotomer interface shown recently to bind GSH in enterovirus F3 and putative antiviral benzene sulphonamide compounds in other enteroviruses. We show, using high-resolution cryo-EM, the binding of a benzene sulphonamide compound with a PV serotype 2 VLP, consistent with antiviral activity through over-stabilizing the interprotomer pocket, preventing the capsid rearrangements necessary for viral infection. Collectively, these results suggest GSH or an analogous tight-binding antiviral offers the potential for stabilizing VLP vaccines.

PubMed: 36434067
DOI: 10.1038/s42003-022-04252-5

Experimental method

ELECTRON MICROSCOPY (2.6 Å)