6DIZ

EV-A71 strain 11316 complexed with tryptophan dendrimer MADAL_0385

6DIZ の概要

• エントリーDOI: 10.2210/pdb6diz/pdb
• EMDBエントリー: 7905 7913
• 分子名称: VP1, VP2, VP3, ... (5 entities in total)
• 機能のキーワード: tryptophan dendrimers, ev-a71, 5-fold vertex, cryo-em, virus
• 由来する生物種: Enterovirus A71; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 94901.99

構造登録者

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. (登録日: 2018-05-24, 公開日: 2019-04-24, 最終更新日: 2024-03-13)

主引用文献

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

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: 31071193
DOI: 10.1371/journal.ppat.1007760

実験手法

ELECTRON MICROSCOPY (3.59 Å)