Structure Elucidation of Coxsackievirus A16 in Complex with GPP3 Informs a Systematic Review of Highly Potent Capsid Binders to Enteroviruses.
The replication of enterovirus 71 (EV71) and coxsackievirus A16 (CVA16), which are the major cause of hand, foot and mouth disease (HFMD) in children, can be inhibited by the capsid binder GPP3. Here, we present the crystal structure of CVA16 in complex with GPP3, which clarifies the role of the key...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-10-01
|
| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1005165 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849726793932603392 |
|---|---|
| author | Luigi De Colibus Xiangxi Wang Aloys Tijsma Johan Neyts John A B Spyrou Jingshan Ren Jonathan M Grimes Gerhard Puerstinger Pieter Leyssen Elizabeth E Fry Zihe Rao David I Stuart |
| author_facet | Luigi De Colibus Xiangxi Wang Aloys Tijsma Johan Neyts John A B Spyrou Jingshan Ren Jonathan M Grimes Gerhard Puerstinger Pieter Leyssen Elizabeth E Fry Zihe Rao David I Stuart |
| author_sort | Luigi De Colibus |
| collection | DOAJ |
| description | The replication of enterovirus 71 (EV71) and coxsackievirus A16 (CVA16), which are the major cause of hand, foot and mouth disease (HFMD) in children, can be inhibited by the capsid binder GPP3. Here, we present the crystal structure of CVA16 in complex with GPP3, which clarifies the role of the key residues involved in interactions with the inhibitor. Based on this model, in silico docking was performed to investigate the interactions with the two next-generation capsid binders NLD and ALD, which we show to be potent inhibitors of a panel of enteroviruses with potentially interesting pharmacological properties. A meta-analysis was performed using the available structural information to obtain a deeper insight into those structural features required for capsid binders to interact effectively and also those that confer broad-spectrum anti-enterovirus activity. |
| format | Article |
| id | doaj-art-d89b91dd3ef940ec81e2edbd8ac8c24a |
| institution | DOAJ |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2015-10-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-d89b91dd3ef940ec81e2edbd8ac8c24a2025-08-20T03:10:05ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742015-10-011110e100516510.1371/journal.ppat.1005165Structure Elucidation of Coxsackievirus A16 in Complex with GPP3 Informs a Systematic Review of Highly Potent Capsid Binders to Enteroviruses.Luigi De ColibusXiangxi WangAloys TijsmaJohan NeytsJohn A B SpyrouJingshan RenJonathan M GrimesGerhard PuerstingerPieter LeyssenElizabeth E FryZihe RaoDavid I StuartThe replication of enterovirus 71 (EV71) and coxsackievirus A16 (CVA16), which are the major cause of hand, foot and mouth disease (HFMD) in children, can be inhibited by the capsid binder GPP3. Here, we present the crystal structure of CVA16 in complex with GPP3, which clarifies the role of the key residues involved in interactions with the inhibitor. Based on this model, in silico docking was performed to investigate the interactions with the two next-generation capsid binders NLD and ALD, which we show to be potent inhibitors of a panel of enteroviruses with potentially interesting pharmacological properties. A meta-analysis was performed using the available structural information to obtain a deeper insight into those structural features required for capsid binders to interact effectively and also those that confer broad-spectrum anti-enterovirus activity.https://doi.org/10.1371/journal.ppat.1005165 |
| spellingShingle | Luigi De Colibus Xiangxi Wang Aloys Tijsma Johan Neyts John A B Spyrou Jingshan Ren Jonathan M Grimes Gerhard Puerstinger Pieter Leyssen Elizabeth E Fry Zihe Rao David I Stuart Structure Elucidation of Coxsackievirus A16 in Complex with GPP3 Informs a Systematic Review of Highly Potent Capsid Binders to Enteroviruses. PLoS Pathogens |
| title | Structure Elucidation of Coxsackievirus A16 in Complex with GPP3 Informs a Systematic Review of Highly Potent Capsid Binders to Enteroviruses. |
| title_full | Structure Elucidation of Coxsackievirus A16 in Complex with GPP3 Informs a Systematic Review of Highly Potent Capsid Binders to Enteroviruses. |
| title_fullStr | Structure Elucidation of Coxsackievirus A16 in Complex with GPP3 Informs a Systematic Review of Highly Potent Capsid Binders to Enteroviruses. |
| title_full_unstemmed | Structure Elucidation of Coxsackievirus A16 in Complex with GPP3 Informs a Systematic Review of Highly Potent Capsid Binders to Enteroviruses. |
| title_short | Structure Elucidation of Coxsackievirus A16 in Complex with GPP3 Informs a Systematic Review of Highly Potent Capsid Binders to Enteroviruses. |
| title_sort | structure elucidation of coxsackievirus a16 in complex with gpp3 informs a systematic review of highly potent capsid binders to enteroviruses |
| url | https://doi.org/10.1371/journal.ppat.1005165 |
| work_keys_str_mv | AT luigidecolibus structureelucidationofcoxsackievirusa16incomplexwithgpp3informsasystematicreviewofhighlypotentcapsidbinderstoenteroviruses AT xiangxiwang structureelucidationofcoxsackievirusa16incomplexwithgpp3informsasystematicreviewofhighlypotentcapsidbinderstoenteroviruses AT aloystijsma structureelucidationofcoxsackievirusa16incomplexwithgpp3informsasystematicreviewofhighlypotentcapsidbinderstoenteroviruses AT johanneyts structureelucidationofcoxsackievirusa16incomplexwithgpp3informsasystematicreviewofhighlypotentcapsidbinderstoenteroviruses AT johnabspyrou structureelucidationofcoxsackievirusa16incomplexwithgpp3informsasystematicreviewofhighlypotentcapsidbinderstoenteroviruses AT jingshanren structureelucidationofcoxsackievirusa16incomplexwithgpp3informsasystematicreviewofhighlypotentcapsidbinderstoenteroviruses AT jonathanmgrimes structureelucidationofcoxsackievirusa16incomplexwithgpp3informsasystematicreviewofhighlypotentcapsidbinderstoenteroviruses AT gerhardpuerstinger structureelucidationofcoxsackievirusa16incomplexwithgpp3informsasystematicreviewofhighlypotentcapsidbinderstoenteroviruses AT pieterleyssen structureelucidationofcoxsackievirusa16incomplexwithgpp3informsasystematicreviewofhighlypotentcapsidbinderstoenteroviruses AT elizabethefry structureelucidationofcoxsackievirusa16incomplexwithgpp3informsasystematicreviewofhighlypotentcapsidbinderstoenteroviruses AT ziherao structureelucidationofcoxsackievirusa16incomplexwithgpp3informsasystematicreviewofhighlypotentcapsidbinderstoenteroviruses AT davidistuart structureelucidationofcoxsackievirusa16incomplexwithgpp3informsasystematicreviewofhighlypotentcapsidbinderstoenteroviruses |