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Publication Abstract from PubMed

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.

A conserved glutathione binding site in poliovirus is a target for antivirals and vaccine stabilisation.,Bahar MW, Nasta V, Fox H, Sherry L, Grehan K, Porta C, Macadam AJ, Stonehouse NJ, Rowlands DJ, Fry EE, Stuart DI Commun Biol. 2022 Nov 25;5(1):1293. doi: 10.1038/s42003-022-04252-5. PMID:36434067^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.