Structure of human enterovirus 71 in complex with a
capsid-binding inhibitor

J 2013

Structure of human enterovirus 71 in complex with a capsid-binding inhibitor

PLEVKA, Pavel, Rushika PERERA, Moh Lan YAP, Jane CARDOSA, Richard KUHN et. al.

Basic information

Original name

Structure of human enterovirus 71 in complex with a capsid-binding inhibitor

Authors

PLEVKA, Pavel, Rushika PERERA, Moh Lan YAP, Jane CARDOSA, Richard KUHN and Michael G. ROSSMANN

Edition

Proceedings of the National Academy of Sciences of the United States of America, WASHINGTON, National Academy of Sciences, 2013, 0027-8424

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10600 1.6 Biological sciences

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 9.809

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1073/pnas.1222379110

UT WoS

000318037800054

Keywords in English

stability; virus

Abstract

V originále

Human enterovirus 71 is a picornavirus causing hand, foot, and mouth disease that may progress to fatal encephalitis in infants and small children. As of now, no cure is available for enterovirus 71 infections. Small molecule inhibitors binding into a hydrophobic pocket within capsid viral protein 1 were previously shown to effectively limit infectivity of many picornaviruses. Here we report a 3.2-angstrom-resolution X-ray structure of the enterovirus 71 virion complexed with the capsid-binding inhibitor WIN 51711. The inhibitor replaced the natural pocket factor within the viral protein 1 pocket without inducing any detectable rearrangements in the structure of the capsid. Furthermore, we show that the compound stabilizes enterovirus 71 virions and limits its infectivity, probably through restricting dynamics of the capsid necessary for genome release. Thus, our results provide a structural basis for development of antienterovirus 71 capsid-binding drugs.

Citovat

PLEVKA, Pavel, Rushika PERERA, Moh Lan YAP, Jane CARDOSA, Richard KUHN and Michael G. ROSSMANN. Structure of human enterovirus 71 in complex with a capsid-binding inhibitor. Proceedings of the National Academy of Sciences of the United States of America. WASHINGTON: National Academy of Sciences, 2013, vol. 110, No 14, p. 5463-5467. ISSN 0027-8424. Available from: https://dx.doi.org/10.1073/pnas.1222379110.

@article{1376802,
   author = {Plevka, Pavel and Perera, Rushika and Yap, Moh Lan and Cardosa, Jane and Kuhn, Richard and Rossmann, Michael G.},
   article_location = {WASHINGTON},
   article_number = {14},
   doi = {http://dx.doi.org/10.1073/pnas.1222379110},
   keywords = {stability; virus},
   language = {eng},
   issn = {0027-8424},
   journal = {Proceedings of the National Academy of Sciences of the United States of America},
   title = {Structure of human enterovirus 71 in complex with a capsid-binding inhibitor},
   volume = {110},
   year = {2013}
}

TY  - JOUR
ID  - 1376802
AU  - Plevka, Pavel - Perera, Rushika - Yap, Moh Lan - Cardosa, Jane - Kuhn, Richard - Rossmann, Michael G.
PY  - 2013
TI  - Structure of human enterovirus 71 in complex with a capsid-binding inhibitor
JF  - Proceedings of the National Academy of Sciences of the United States of America
VL  - 110
IS  - 14
SP  - 5463-5467
EP  - 5463-5467
PB  - National Academy of Sciences
SN  - 00278424
KW  - stability
KW  - virus
N2  - Human enterovirus 71 is a picornavirus causing hand, foot, and mouth disease that may progress to fatal encephalitis in infants and small children. As of now, no cure is available for enterovirus 71 infections. Small molecule inhibitors binding into a hydrophobic pocket within capsid viral protein 1 were previously shown to effectively limit infectivity of many picornaviruses. Here we report a 3.2-angstrom-resolution X-ray structure of the enterovirus 71 virion complexed with the capsid-binding inhibitor WIN 51711. The inhibitor replaced the natural pocket factor within the viral protein 1 pocket without inducing any detectable rearrangements in the structure of the capsid. Furthermore, we show that the compound stabilizes enterovirus 71 virions and limits its infectivity, probably through restricting dynamics of the capsid necessary for genome release. Thus, our results provide a structural basis for development of antienterovirus 71 capsid-binding drugs.
ER  -

PLEVKA, Pavel, Rushika PERERA, Moh Lan YAP, Jane CARDOSA, Richard KUHN and Michael G. ROSSMANN. Structure of human enterovirus 71 in complex with a capsid-binding inhibitor. \textit{Proceedings of the National Academy of Sciences of the United States of America}. WASHINGTON: National Academy of Sciences, 2013, vol.~110, No~14, p.~5463-5467. ISSN~0027-8424. Available from: https://dx.doi.org/10.1073/pnas.1222379110.

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