6DIZ
EV-A71 strain 11316 complexed with tryptophan dendrimer MADAL_0385
Summary for 6DIZ
| Entry DOI | 10.2210/pdb6diz/pdb |
| EMDB information | 7905 7913 |
| Descriptor | VP1, VP2, VP3, ... (5 entities in total) |
| Functional Keywords | tryptophan dendrimers, ev-a71, 5-fold vertex, cryo-em, virus |
| Biological source | Enterovirus A71 More |
| Total number of polymer chains | 4 |
| Total formula weight | 94901.99 |
| Authors | Sun, L.,Lee, H.,Thibaut, H.J.,Rivero-Buceta, E.,Martinez-Gualda, B.,Delang, L.,Leyssen, P.,Gago, F.,San-Felix, A.,Hafenstein, S.,Mirabelli, C.,Neyts, J. (deposition date: 2018-05-24, release date: 2019-04-24, Last modification date: 2024-03-13) |
| Primary citation | Sun, L.,Lee, H.,Thibaut, H.J.,Lanko, K.,Rivero-Buceta, E.,Bator, C.,Martinez-Gualda, B.,Dallmeier, K.,Delang, L.,Leyssen, P.,Gago, F.,San-Felix, A.,Hafenstein, S.,Mirabelli, C.,Neyts, J. Viral engagement with host (co-)receptors blocked by a novel class of tryptophan dendrimers that targets the 5-fold-axis of the enterovirus-A71 capsid. Plos Pathog., 15:e1007760-e1007760, 2019 Cited by PubMed Abstract: Enterovirus A71 (EV-A71) is a non-polio neurotropic enterovirus with pandemic potential. There are no antiviral agents approved to prevent or treat EV-A71 infections. We here report on the molecular mechanism by which a novel class of tryptophan dendrimers inhibits (at low nanomolar to high picomolar concentration) EV-A71 replication in vitro. A lead compound in the series (MADAL385) prevents binding and internalization of the virus but does not, unlike classical capsid binders, stabilize the particle. By means of resistance selection, reverse genetics and cryo-EM, we map the binding region of MADAL385 to the 5-fold vertex of the viral capsid and demonstrate that a single molecule binds to each vertex. By interacting with this region, MADAL385 prevents the interaction of the virus with its cellular receptors PSGL1 and heparan sulfate, thereby blocking the attachment of EV-A71 to the host cells. PubMed: 31071193DOI: 10.1371/journal.ppat.1007760 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.59 Å) |
Structure validation
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