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dc.contributor.authorAlam, Intikhab
dc.contributor.authorKamau, Allan
dc.contributor.authorKulmanov, Maxat
dc.contributor.authorJaremko, Lukasz
dc.contributor.authorArold, Stefan T.
dc.contributor.authorPain, Arnab
dc.contributor.authorGojobori, Takashi
dc.contributor.authorDuarte, Carlos M.
dc.date.accessioned2020-07-27T06:48:02Z
dc.date.available2020-03-02T08:57:59Z
dc.date.available2020-03-09T13:00:35Z
dc.date.available2020-07-01T13:56:17Z
dc.date.available2020-07-27T06:48:02Z
dc.date.issued2020-06-30
dc.identifier.citationAlam, I., Kamau, A. K., Kulmanov, M., Arold, S. T., Pain, A. T., Gojobori, T., & Duarte, C. M. (2020). Functional pangenome analysis points to protein E, a pathogenicity determinant in SARS, as a therapeutic target for COVID-19 complications. doi:10.3389/fcimb.2020.00405
dc.identifier.issn2235-2988
dc.identifier.doi10.3389/fcimb.2020.00405
dc.identifier.doi10.1101/2020.02.17.952895
dc.identifier.urihttp://hdl.handle.net/10754/661831
dc.description.abstractThe spread of the novel coronavirus (SARS-CoV-2) has triggered a global emergency, that demands urgent solutions for detection and therapy to prevent escalating health, social, and economic impacts. The spike protein (S) of this virus enables binding to the human receptor ACE2, and hence presents a prime target for vaccines preventing viral entry into host cells. The S proteins from SARS and SARS-CoV-2 are similar, but structural differences in the receptor binding domain (RBD) preclude the use of SARS-specific neutralizing antibodies to inhibit SARS-CoV-2. Here we used comparative pangenomic analysis of all sequenced reference Betacoronaviruses, complemented with functional and structural analyses. This analysis reveals that, among all core gene clusters present in these viruses, the envelope protein E shows a variant cluster shared by SARS and SARS-CoV-2 with two completely-conserved key functional features, namely an ion-channel, and a PDZ-binding motif (PBM). These features play a key role in the activation of the inflammasome causing the acute respiratory distress syndrome, the leading cause of death in SARS and SARS-CoV-2 infections. Together with functional pangenomic analysis, mutation tracking, and previous evidence, on E protein as a determinant of pathogenicity in SARS, we suggest E protein as an alternative therapeutic target to be considered for further studies to reduce complications of SARS-CoV-2 infections in COVID-19.
dc.description.sponsorshipThe research reported in this publication was supported by funding from King Abdullah University of Science and Technology (KAUST), under award number FCC/1/1976-25-01.
dc.description.sponsorshipWe are thankful to KAUST Supercomputing Laboratory (KSL), KAUST Information Technology (IT) and Muhammad Saif from CBRC, KAUST for providing support in computing resources. We are grateful to all the authors and GSAID for providing access to SARS-CoV-2 isolates for research, contributing labs and authors are clearly shown in the metadata table at https://trackncov.cbrc.kaust.edu.sa.
dc.publisherFrontiers
dc.relation.urlhttps://www.frontiersin.org/articles/10.3389/fcimb.2020.00405/abstract
dc.rights© 2020 Alam, Kamau, Kulmanov, Jaremko, Arold, Pain, Gojobori and Duarte. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleFunctional Pangenome Analysis Shows Key Features of E Protein Are Preserved in SARS and SARS-CoV-2
dc.typeArticle
dc.contributor.departmentComputational Bioscience Research Center (CBRC)
dc.contributor.departmentComputer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division
dc.contributor.departmentComputer Science Program
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Division
dc.contributor.departmentBioscience Program
dc.contributor.departmentMarine Science Program
dc.contributor.departmentRed Sea Research Center (RSRC)
dc.identifier.journalFrontiers in Cellular and Infection Microbiology
dc.eprint.versionPublisher's Version/PDF
dc.contributor.institutionCentre de Biochimie Structurale, CNRS, INSERM, Université de Montpellier, Montpellier, France
dc.contributor.institutionResearch Center for Zoonosis Control, Hokkaido University, Sapporo, Japan
dc.identifier.volume10
pubs.publication-statusPublisheden_US
kaust.personAlam, Intikhab
kaust.personKamau, Allan
kaust.personKulmanov, Maxat
kaust.personJaremko, Lukasz
kaust.personArold, Stefan T.
kaust.personPain, Arnab
kaust.personGojobori, Takashi
kaust.personDuarte, Carlos M.
kaust.grant.numberFCC/1/1976-25-01
dc.relation.issupplementedbyURL:https://pangenomedb.cbrc.kaust.edu.sa/
refterms.dateFOA2020-03-02T08:59:01Z
display.relations<b> Is Supplemented By:</b> <br/> <ul><li><i>[Database]</i> <br/> Betacoronavirus PanGenome DB. URL: <a href="https://pangenomedb.cbrc.kaust.edu.sa/">https://pangenomedb.cbrc.kaust.edu.sa/</a></li></ul>
kaust.acknowledged.supportUnitKAUST Supercomputing Laboratory (KSL)
kaust.acknowledged.supportUnitKAUST Information Technology (IT)
kaust.acknowledged.supportUnitKAUST Information Technology (IT)
dc.date.posted2020-03-06


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© 2020 Alam, Kamau, Kulmanov, Jaremko, Arold, Pain, Gojobori and Duarte. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Except where otherwise noted, this item's license is described as © 2020 Alam, Kamau, Kulmanov, Jaremko, Arold, Pain, Gojobori and Duarte. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
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