6GZV
Identification of a druggable VP1-VP3 interprotomer pocket in the capsid of enteroviruses
Summary for 6GZV
| Entry DOI | 10.2210/pdb6gzv/pdb |
| EMDB information | 0103 |
| Descriptor | Capsid protein VP1, Capsid protein VP2, Capsid protein VP3, ... (5 entities in total) |
| Functional Keywords | inhibitor, complex, virus |
| Biological source | Coxsackievirus B3 (strain Nancy) More |
| Total number of polymer chains | 4 |
| Total formula weight | 94674.45 |
| Authors | Geraets, J.A.,Flatt, J.W.,Domanska, A.,Butcher, S.J. (deposition date: 2018-07-05, release date: 2019-06-05, Last modification date: 2024-05-15) |
| Primary citation | Abdelnabi, R.,Geraets, J.A.,Ma, Y.,Mirabelli, C.,Flatt, J.W.,Domanska, A.,Delang, L.,Jochmans, D.,Kumar, T.A.,Jayaprakash, V.,Sinha, B.N.,Leyssen, P.,Butcher, S.J.,Neyts, J. A novel druggable interprotomer pocket in the capsid of rhino- and enteroviruses. Plos Biol., 17:e3000281-e3000281, 2019 Cited by PubMed Abstract: Rhino- and enteroviruses are important human pathogens, against which no antivirals are available. The best-studied inhibitors are "capsid binders" that fit in a hydrophobic pocket of the viral capsid. Employing a new class of entero-/rhinovirus inhibitors and by means of cryo-electron microscopy (EM), followed by resistance selection and reverse genetics, we discovered a hitherto unknown druggable pocket that is formed by viral proteins VP1 and VP3 and that is conserved across entero-/rhinovirus species. We propose that these inhibitors stabilize a key region of the virion, thereby preventing the conformational expansion needed for viral RNA release. A medicinal chemistry effort resulted in the identification of analogues targeting this pocket with broad-spectrum activity against Coxsackieviruses B (CVBs) and compounds with activity against enteroviruses (EV) of groups C and D, and even rhinoviruses (RV). Our findings provide novel insights in the biology of the entry of entero-/rhinoviruses and open new avenues for the design of broad-spectrum antivirals against these pathogens. PubMed: 31185007DOI: 10.1371/journal.pbio.3000281 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (4 Å) |
Structure validation
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