CovidFranceV1, Main, Exploration, bibRecord, 000F08

Functional Pangenome Analysis Shows Key Features of E Protein Are Preserved in SARS and SARS-CoV-2.

Identifieur interne : 000F08 ( Main/Exploration ); précédent : 000F07; suivant : 000F09

Functional Pangenome Analysis Shows Key Features of E Protein Are Preserved in SARS and SARS-CoV-2.

Auteurs : Intikhab Alam [Arabie saoudite] ; Allan A. Kamau [Arabie saoudite] ; Maxat Kulmanov [Arabie saoudite] ; Łukasz Jaremko [Arabie saoudite] ; Stefan T. Arold [Arabie saoudite, France] ; Arnab Pain [Arabie saoudite, Japon] ; Takashi Gojobori [Arabie saoudite] ; Carlos M. Duarte [Arabie saoudite]

Source :

Frontiers in cellular and infection microbiology [ 2235-2988 ] ; 2020.

RBID : pubmed:32850499

Descripteurs français

English descriptors

KwdEn :
- Betacoronavirus (chemistry), Coronavirus Infections (virology), Genes, Essential (MeSH), Genes, Viral (MeSH), Genome, Viral (MeSH), Humans (MeSH), Middle East Respiratory Syndrome Coronavirus (chemistry), Middle East Respiratory Syndrome Coronavirus (genetics), Mutation (MeSH), Open Reading Frames (MeSH), PDZ Domains (MeSH), Pandemics (MeSH), Pneumonia, Viral (virology), Protein Domains (MeSH), SARS Virus (chemistry), Viral Envelope Proteins (chemistry), Viral Envelope Proteins (genetics).
MESH :
- chemical , chemistry : Viral Envelope Proteins.
- chemistry : Betacoronavirus, Middle East Respiratory Syndrome Coronavirus, SARS Virus.
- genetics : Middle East Respiratory Syndrome Coronavirus, Viral Envelope Proteins.
- virology : Coronavirus Infections, Pneumonia, Viral.
- Genes, Essential, Genes, Viral, Genome, Viral, Humans, Mutation, Open Reading Frames, PDZ Domains, Pandemics, Protein Domains.

Abstract

The 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.

DOI: 10.3389/fcimb.2020.00405
PubMed: 32850499
PubMed Central: PMC7396417

Affiliations:

Links toward previous steps (curation, corpus...)

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Le document en format XML

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<term>Genes, Viral (MeSH)</term>
<term>Genome, Viral (MeSH)</term>
<term>Humans (MeSH)</term>
<term>Middle East Respiratory Syndrome Coronavirus (chemistry)</term>
<term>Middle East Respiratory Syndrome Coronavirus (genetics)</term>
<term>Mutation (MeSH)</term>
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<term>SARS Virus (chemistry)</term>
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<term>Domaines PDZ (MeSH)</term>
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<term>Génome viral (MeSH)</term>
<term>Humains (MeSH)</term>
<term>Infections à coronavirus (virologie)</term>
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<term>Protéines de l'enveloppe virale (génétique)</term>
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<front><div type="abstract" xml:lang="en">The 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 <i>Betacoronaviruses</i>
, 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.</div>
</front>
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<Title>Frontiers in cellular and infection microbiology</Title>
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<Abstract><AbstractText>The 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 <i>Betacoronaviruses</i>
, 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.</AbstractText>
<CopyrightInformation>Copyright © 2020 Alam, Kamau, Kulmanov, Jaremko, Arold, Pain, Gojobori and Duarte.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Alam</LastName>
<ForeName>Intikhab</ForeName>
<Initials>I</Initials>
<AffiliationInfo><Affiliation>Biological and Environmental Science and Engineering (BESE), Computational Bioscience Research Center (CBRC), King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia.</Affiliation>
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<Author ValidYN="Y"><LastName>Kamau</LastName>
<ForeName>Allan A</ForeName>
<Initials>AA</Initials>
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<Author ValidYN="Y"><LastName>Kulmanov</LastName>
<ForeName>Maxat</ForeName>
<Initials>M</Initials>
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</AffiliationInfo>
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<Author ValidYN="Y"><LastName>Jaremko</LastName>
<ForeName>Łukasz</ForeName>
<Initials>Ł</Initials>
<AffiliationInfo><Affiliation>Biological and Environmental Science and Engineering (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia.</Affiliation>
</AffiliationInfo>
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<Author ValidYN="Y"><LastName>Arold</LastName>
<ForeName>Stefan T</ForeName>
<Initials>ST</Initials>
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Functional Pangenome Analysis Shows Key Features of E Protein Are Preserved in SARS and SARS-CoV-2.

Functional Pangenome Analysis Shows Key Features of E Protein Are Preserved in SARS and SARS-CoV-2.

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