Illustrating and homology modeling the proteins of the Zika virus [version 2; referees: 2 approved]
The Zika virus (ZIKV) is a flavivirus of the family Flaviviridae, which is similar to dengue virus, yellow fever and West Nile virus. Recent outbreaks in South America, Latin America, the Caribbean and in particular Brazil have led to concern for the spread of the disease and potential to cause Guil...
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doaj-368ebe88be504dacb55be77ac35cc09b2020-11-25T03:50:52ZengF1000 Research LtdF1000Research2046-14022016-09-01510.12688/f1000research.8213.210258Illustrating and homology modeling the proteins of the Zika virus [version 2; referees: 2 approved]Sean Ekins0John Liebler1Bruno J. Neves2Warren G. Lewis3Megan Coffee4Rachelle Bienstock5Christopher Southan6Carolina H. Andrade7Collaborations in Chemistry, Fuquay-Varina, NC, USAArt of the Cell, Guilford, CT, USALabMol - Laboratory for Molecular Modeling and Drug Design, Faculty of Pharmacy, Federal University of Goias, GO, BrazilDepartment of Medicine, Washington University School of Medicine, St Louis, MO, USAThe International Rescue Committee, New York, NY, USARJB Computational Modeling LLC, Chapel Hill, NC, USACentre for Integrative Physiology, University of Edinburgh, Edinburgh, UKLabMol - Laboratory for Molecular Modeling and Drug Design, Faculty of Pharmacy, Federal University of Goias, GO, BrazilThe Zika virus (ZIKV) is a flavivirus of the family Flaviviridae, which is similar to dengue virus, yellow fever and West Nile virus. Recent outbreaks in South America, Latin America, the Caribbean and in particular Brazil have led to concern for the spread of the disease and potential to cause Guillain-Barré syndrome and microcephaly. Although ZIKV has been known of for over 60 years there is very little in the way of knowledge of the virus with few publications and no crystal structures. No antivirals have been tested against it either in vitro or in vivo. ZIKV therefore epitomizes a neglected disease. Several suggested steps have been proposed which could be taken to initiate ZIKV antiviral drug discovery using both high throughput screens as well as structure-based design based on homology models for the key proteins. We now describe preliminary homology models created for NS5, FtsJ, NS4B, NS4A, HELICc, DEXDc, peptidase S7, NS2B, NS2A, NS1, E stem, glycoprotein M, propeptide, capsid and glycoprotein E using SWISS-MODEL. Eleven out of 15 models pass our model quality criteria for their further use. While a ZIKV glycoprotein E homology model was initially described in the immature conformation as a trimer, we now describe the mature dimer conformer which allowed the construction of an illustration of the complete virion. By comparing illustrations of ZIKV based on this new homology model and the dengue virus crystal structure we propose potential differences that could be exploited for antiviral and vaccine design. The prediction of sites for glycosylation on this protein may also be useful in this regard. While we await a cryo-EM structure of ZIKV and eventual crystal structures of the individual proteins, these homology models provide the community with a starting point for structure-based design of drugs and vaccines as well as a for computational virtual screening.http://f1000research.com/articles/5-275/v2Drug Discovery & DesignMacromolecular ChemistryProtein Chemistry & ProteomicsTropical & Travel-Associated Diseases |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sean Ekins John Liebler Bruno J. Neves Warren G. Lewis Megan Coffee Rachelle Bienstock Christopher Southan Carolina H. Andrade |
spellingShingle |
Sean Ekins John Liebler Bruno J. Neves Warren G. Lewis Megan Coffee Rachelle Bienstock Christopher Southan Carolina H. Andrade Illustrating and homology modeling the proteins of the Zika virus [version 2; referees: 2 approved] F1000Research Drug Discovery & Design Macromolecular Chemistry Protein Chemistry & Proteomics Tropical & Travel-Associated Diseases |
author_facet |
Sean Ekins John Liebler Bruno J. Neves Warren G. Lewis Megan Coffee Rachelle Bienstock Christopher Southan Carolina H. Andrade |
author_sort |
Sean Ekins |
title |
Illustrating and homology modeling the proteins of the Zika virus [version 2; referees: 2 approved] |
title_short |
Illustrating and homology modeling the proteins of the Zika virus [version 2; referees: 2 approved] |
title_full |
Illustrating and homology modeling the proteins of the Zika virus [version 2; referees: 2 approved] |
title_fullStr |
Illustrating and homology modeling the proteins of the Zika virus [version 2; referees: 2 approved] |
title_full_unstemmed |
Illustrating and homology modeling the proteins of the Zika virus [version 2; referees: 2 approved] |
title_sort |
illustrating and homology modeling the proteins of the zika virus [version 2; referees: 2 approved] |
publisher |
F1000 Research Ltd |
series |
F1000Research |
issn |
2046-1402 |
publishDate |
2016-09-01 |
description |
The Zika virus (ZIKV) is a flavivirus of the family Flaviviridae, which is similar to dengue virus, yellow fever and West Nile virus. Recent outbreaks in South America, Latin America, the Caribbean and in particular Brazil have led to concern for the spread of the disease and potential to cause Guillain-Barré syndrome and microcephaly. Although ZIKV has been known of for over 60 years there is very little in the way of knowledge of the virus with few publications and no crystal structures. No antivirals have been tested against it either in vitro or in vivo. ZIKV therefore epitomizes a neglected disease. Several suggested steps have been proposed which could be taken to initiate ZIKV antiviral drug discovery using both high throughput screens as well as structure-based design based on homology models for the key proteins. We now describe preliminary homology models created for NS5, FtsJ, NS4B, NS4A, HELICc, DEXDc, peptidase S7, NS2B, NS2A, NS1, E stem, glycoprotein M, propeptide, capsid and glycoprotein E using SWISS-MODEL. Eleven out of 15 models pass our model quality criteria for their further use. While a ZIKV glycoprotein E homology model was initially described in the immature conformation as a trimer, we now describe the mature dimer conformer which allowed the construction of an illustration of the complete virion. By comparing illustrations of ZIKV based on this new homology model and the dengue virus crystal structure we propose potential differences that could be exploited for antiviral and vaccine design. The prediction of sites for glycosylation on this protein may also be useful in this regard. While we await a cryo-EM structure of ZIKV and eventual crystal structures of the individual proteins, these homology models provide the community with a starting point for structure-based design of drugs and vaccines as well as a for computational virtual screening. |
topic |
Drug Discovery & Design Macromolecular Chemistry Protein Chemistry & Proteomics Tropical & Travel-Associated Diseases |
url |
http://f1000research.com/articles/5-275/v2 |
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