Structural insight into the role of novel SARS-CoV-2 E protein: A potential target for vaccine development and other therapeutic strategies
The outbreak of COVID-19 across the world has posed unprecedented and global challenges on multiple fronts. Most of the vaccine and drug development has focused on the spike proteins and viral RNA-polymerases and main protease for viral replication. Using the bioinformatics and structural modelling...
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| description | The outbreak of COVID-19 across the world has posed unprecedented and global challenges on multiple fronts. Most of the vaccine and drug development has focused on the spike proteins and viral RNA-polymerases and main protease for viral replication. Using the bioinformatics and structural modelling approach, we modelled the structure of the envelope (E)-protein of novel SARS-CoV-2. The E-protein of this virus shares sequence similarity with that of SARS- CoV-1, and is highly conserved in the N-terminus regions. Incidentally, compared to spike proteins, E proteins demonstrate lower disparity and mutability among the isolated sequences. Using homology modelling, we found that the most favorable structure could function as a gated ion channel conducting H+ ions. Combining pocket estimation and docking with water, we determined that GLU 8 and ASN 15 in the N-terminal region were in close proximity to form H-bonds which was further validated by insertion of the E protein in an ERGIC-mimic membrane. Additionally, two distinct "core" structures were visible, the hydrophobic core and the central core, which may regulate the opening/closing of the channel. We propose this as a mechanism of viral ion channeling activity which plays a critical role in viral infection and pathogenesis. In addition, it provides a structural basis and additional avenues for vaccine development and generating therapeutic interventions against the virus. |
| doi_str_mv | 10.1371/journal.pone.0237300 |
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Most of the vaccine and drug development has focused on the spike proteins and viral RNA-polymerases and main protease for viral replication. Using the bioinformatics and structural modelling approach, we modelled the structure of the envelope (E)-protein of novel SARS-CoV-2. The E-protein of this virus shares sequence similarity with that of SARS- CoV-1, and is highly conserved in the N-terminus regions. Incidentally, compared to spike proteins, E proteins demonstrate lower disparity and mutability among the isolated sequences. Using homology modelling, we found that the most favorable structure could function as a gated ion channel conducting H+ ions. Combining pocket estimation and docking with water, we determined that GLU 8 and ASN 15 in the N-terminal region were in close proximity to form H-bonds which was further validated by insertion of the E protein in an ERGIC-mimic membrane. Additionally, two distinct "core" structures were visible, the hydrophobic core and the central core, which may regulate the opening/closing of the channel. We propose this as a mechanism of viral ion channeling activity which plays a critical role in viral infection and pathogenesis. In addition, it provides a structural basis and additional avenues for vaccine development and generating therapeutic interventions against the virus.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0237300</identifier><identifier>PMID: 32785274</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Betacoronavirus - chemistry ; Betacoronavirus - isolation & purification ; Bioinformatics ; Biology and life sciences ; Channeling ; Computer Simulation ; Conserved sequence ; Coronavirus Envelope Proteins ; Coronavirus Infections - prevention & control ; Coronavirus Infections - virology ; Coronaviruses ; COVID-19 ; COVID-19 Vaccines ; Development and progression ; Drug development ; Homology ; Humans ; Hydrogen ; Hydrogen Bonding ; Hydrophobicity ; Insertion ; Ion channels ; Magnetic Resonance Spectroscopy ; Medical research ; Medicine and health sciences ; Membrane proteins ; Modelling ; Models, Molecular ; Mortality ; Mutation ; N-Terminus ; Pandemics - prevention & control ; Pathogenesis ; Physiological aspects ; Pneumonia, Viral - prevention & control ; Pneumonia, Viral - virology ; Point Mutation ; Prevention ; Protein Conformation ; Proteins ; Research and Analysis Methods ; Ribonucleic acid ; RNA ; SARS-CoV-2 ; Severe acute respiratory syndrome ; Severe acute respiratory syndrome coronavirus 2 ; Structural Homology, Protein ; Structure ; Structure-function relationships ; Therapeutic applications ; Vaccine development ; Vaccines ; Vaccines, Attenuated ; Vaccines, Inactivated ; Viral diseases ; Viral envelope proteins ; Viral Envelope Proteins - chemistry ; Viral Envelope Proteins - genetics ; Viral Envelope Proteins - immunology ; Viral proteins ; Viral Vaccines ; Viruses ; Water - chemistry</subject><ispartof>PloS one, 2020-08, Vol.15 (8), p.e0237300-e0237300</ispartof><rights>COPYRIGHT 2020 Public Library of Science</rights><rights>2020 Sarkar, Saha. 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Most of the vaccine and drug development has focused on the spike proteins and viral RNA-polymerases and main protease for viral replication. Using the bioinformatics and structural modelling approach, we modelled the structure of the envelope (E)-protein of novel SARS-CoV-2. The E-protein of this virus shares sequence similarity with that of SARS- CoV-1, and is highly conserved in the N-terminus regions. Incidentally, compared to spike proteins, E proteins demonstrate lower disparity and mutability among the isolated sequences. Using homology modelling, we found that the most favorable structure could function as a gated ion channel conducting H+ ions. Combining pocket estimation and docking with water, we determined that GLU 8 and ASN 15 in the N-terminal region were in close proximity to form H-bonds which was further validated by insertion of the E protein in an ERGIC-mimic membrane. 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chemistry</subject><subject>Viral Envelope Proteins - genetics</subject><subject>Viral Envelope Proteins - immunology</subject><subject>Viral proteins</subject><subject>Viral Vaccines</subject><subject>Viruses</subject><subject>Water - chemistry</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk9-KEzEUxgdR3LX6BqIBQfSiNX9mJq0XQimrFhYWtrq3IZM5M02ZTmaTTNFn8KU93c4ureyF5CIh-X1fki85SfKa0QkTkn3auN63upl0roUJ5UIKSp8k52wm-DjnVDw9Gp8lL0LYUJqJaZ4_T84El9OMy_Q8-bOKvjex97ohtg22XkfsoyNxDcS7BoirSOt20JDV_Ho1XribMScXpPMugm0_kznpcNRGiwZR-xoiqZwnO22MbYGUgFLXbZEgui2JQ1-_N_e6gz5aQ0L0OkJtIbxMnlW6CfBq6EfJz68XPxbfx5dX35aL-eXY5JzHcSlMOgVezCSwPC2Z0KXI09RklM2Y5jQrWEZ5ZUoppUBI8MyIghk2y2eFFlSMkrcH365xQQ05BsVTIXiKUI7E8kCUTm9U5-1W-9_KaavuJpyvlfZ4-AZUCpxVRcHzXEA6FYWujM4yqbO8YCXLpuj1ZditL7ZQGkwCwz4xPV1p7VrVbqdkygXDhx0lHwYD7257CFFtbTDQNLoF19-dO6WZlJlE9N0_6OO3G6ha4wVsWznc1-xN1TwXXFBMc4bU5BEKWwlba_DTVRbnTwQfTwTIRPgVa92HoJar6_9nr25O2fdH7Bp0E9fBNfh5XBtOwfQAGu9C8FA9hMyo2tfMfRpqXzNqqBmUvTl-oAfRfZGIv8uREX8</recordid><startdate>20200812</startdate><enddate>20200812</enddate><creator>Sarkar, Manish</creator><creator>Saha, Soham</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>COVID</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0003-1173-1397</orcidid></search><sort><creationdate>20200812</creationdate><title>Structural insight into the role of novel SARS-CoV-2 E protein: A potential target for vaccine development and other therapeutic strategies</title><author>Sarkar, Manish ; Saha, Soham</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c622t-d3c48e2b97e164d13ad3644c50191a205b1502fcd777397e325c3b1c1969ba303</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Betacoronavirus - chemistry</topic><topic>Betacoronavirus - isolation & purification</topic><topic>Bioinformatics</topic><topic>Biology and life sciences</topic><topic>Channeling</topic><topic>Computer Simulation</topic><topic>Conserved sequence</topic><topic>Coronavirus Envelope Proteins</topic><topic>Coronavirus Infections - prevention & control</topic><topic>Coronavirus Infections - virology</topic><topic>Coronaviruses</topic><topic>COVID-19</topic><topic>COVID-19 Vaccines</topic><topic>Development and progression</topic><topic>Drug development</topic><topic>Homology</topic><topic>Humans</topic><topic>Hydrogen</topic><topic>Hydrogen Bonding</topic><topic>Hydrophobicity</topic><topic>Insertion</topic><topic>Ion channels</topic><topic>Magnetic Resonance Spectroscopy</topic><topic>Medical research</topic><topic>Medicine and health sciences</topic><topic>Membrane proteins</topic><topic>Modelling</topic><topic>Models, Molecular</topic><topic>Mortality</topic><topic>Mutation</topic><topic>N-Terminus</topic><topic>Pandemics - 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Most of the vaccine and drug development has focused on the spike proteins and viral RNA-polymerases and main protease for viral replication. Using the bioinformatics and structural modelling approach, we modelled the structure of the envelope (E)-protein of novel SARS-CoV-2. The E-protein of this virus shares sequence similarity with that of SARS- CoV-1, and is highly conserved in the N-terminus regions. Incidentally, compared to spike proteins, E proteins demonstrate lower disparity and mutability among the isolated sequences. Using homology modelling, we found that the most favorable structure could function as a gated ion channel conducting H+ ions. Combining pocket estimation and docking with water, we determined that GLU 8 and ASN 15 in the N-terminal region were in close proximity to form H-bonds which was further validated by insertion of the E protein in an ERGIC-mimic membrane. Additionally, two distinct "core" structures were visible, the hydrophobic core and the central core, which may regulate the opening/closing of the channel. We propose this as a mechanism of viral ion channeling activity which plays a critical role in viral infection and pathogenesis. In addition, it provides a structural basis and additional avenues for vaccine development and generating therapeutic interventions against the virus.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>32785274</pmid><doi>10.1371/journal.pone.0237300</doi><orcidid>https://orcid.org/0000-0003-1173-1397</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | PloS one, 2020-08, Vol.15 (8), p.e0237300-e0237300 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2433249696 |
| source | PubMed Central (Open Access); MEDLINE; Public Library of Science; Full-Text Journals in Chemistry (Open access); DOAJ Directory of Open Access Journals; EZB Electronic Journals Library |
| subjects | Betacoronavirus - chemistry Betacoronavirus - isolation & purification Bioinformatics Biology and life sciences Channeling Computer Simulation Conserved sequence Coronavirus Envelope Proteins Coronavirus Infections - prevention & control Coronavirus Infections - virology Coronaviruses COVID-19 COVID-19 Vaccines Development and progression Drug development Homology Humans Hydrogen Hydrogen Bonding Hydrophobicity Insertion Ion channels Magnetic Resonance Spectroscopy Medical research Medicine and health sciences Membrane proteins Modelling Models, Molecular Mortality Mutation N-Terminus Pandemics - prevention & control Pathogenesis Physiological aspects Pneumonia, Viral - prevention & control Pneumonia, Viral - virology Point Mutation Prevention Protein Conformation Proteins Research and Analysis Methods Ribonucleic acid RNA SARS-CoV-2 Severe acute respiratory syndrome Severe acute respiratory syndrome coronavirus 2 Structural Homology, Protein Structure Structure-function relationships Therapeutic applications Vaccine development Vaccines Vaccines, Attenuated Vaccines, Inactivated Viral diseases Viral envelope proteins Viral Envelope Proteins - chemistry Viral Envelope Proteins - genetics Viral Envelope Proteins - immunology Viral proteins Viral Vaccines Viruses Water - chemistry |
| title | Structural insight into the role of novel SARS-CoV-2 E protein: A potential target for vaccine development and other therapeutic strategies |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-07T18%3A58%3A17IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Structural%20insight%20into%20the%20role%20of%20novel%20SARS-CoV-2%20E%20protein:%20A%20potential%20target%20for%20vaccine%20development%20and%20other%20therapeutic%20strategies&rft.jtitle=PloS%20one&rft.au=Sarkar,%20Manish&rft.date=2020-08-12&rft.volume=15&rft.issue=8&rft.spage=e0237300&rft.epage=e0237300&rft.pages=e0237300-e0237300&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0237300&rft_dat=%3Cgale_plos_%3EA632306449%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2433249696&rft_id=info:pmid/32785274&rft_galeid=A632306449&rft_doaj_id=oai_doaj_org_article_4e21fbb2663e483bafca557a56b1d158&rfr_iscdi=true |