Unrevealing sequence and structural features of novel coronavirus using in silico approaches: The main protease as molecular target
Identifieur interne : 000009 ( Pmc/Checkpoint ); précédent : 000008; suivant : 000010Unrevealing sequence and structural features of novel coronavirus using in silico approaches: The main protease as molecular target
Auteurs : Joseph Thomas Ortega [États-Unis] ; Maria Luisa Serrano [Venezuela] ; Flor Helene Pujol [Venezuela] ; Hector Rafael Rangel [Venezuela]Source :
- EXCLI Journal [ 1611-2156 ] ; 2020.
Abstract
Direct-acting antivirals are effective tools to control viral infections. SARS-CoV-2 is a coronavirus associated with the epidemiological outbreak in late 2019. Previous reports showed that HIV-1 protease inhibitors could block SARS-CoV main protease. Based on that and using an
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DOI: 10.17179/excli2020-1189
PubMed: NONE
PubMed Central: 7081067
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Unrevealing sequence and structural features of novel coronavirus using <italic>in silico</italic> approaches: The main protease as molecular target</title><author><name sortKey="Ortega, Joseph Thomas" sort="Ortega, Joseph Thomas" uniqKey="Ortega J" first="Joseph Thomas" last="Ortega">Joseph Thomas Ortega</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Pharmacology and Cleveland Center for Membrane and Structural Biology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pharmacology and Cleveland Center for Membrane and Structural Biology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Serrano, Maria Luisa" sort="Serrano, Maria Luisa" uniqKey="Serrano M" first="Maria Luisa" last="Serrano">Maria Luisa Serrano</name><affiliation wicri:level="1"><nlm:aff id="A2">Unidad de Química Medicinal, Facultad de Farmacia, Universidad Central de Venezuela, Caracas, Venezuela</nlm:aff><country xml:lang="fr">Venezuela</country><wicri:regionArea>Unidad de Química Medicinal, Facultad de Farmacia, Universidad Central de Venezuela, Caracas</wicri:regionArea><wicri:noRegion>Caracas</wicri:noRegion></affiliation></author><author><name sortKey="Pujol, Flor Helene" sort="Pujol, Flor Helene" uniqKey="Pujol F" first="Flor Helene" last="Pujol">Flor Helene Pujol</name><affiliation wicri:level="1"><nlm:aff id="A3">Laboratorio de Virología Molecular, Centro de Microbiología y Biología Celular, Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela</nlm:aff><country xml:lang="fr">Venezuela</country><wicri:regionArea>Laboratorio de Virología Molecular, Centro de Microbiología y Biología Celular, Instituto Venezolano de Investigaciones Científicas, Caracas</wicri:regionArea><wicri:noRegion>Caracas</wicri:noRegion></affiliation></author><author><name sortKey="Rangel, Hector Rafael" sort="Rangel, Hector Rafael" uniqKey="Rangel H" first="Hector Rafael" last="Rangel">Hector Rafael Rangel</name><affiliation wicri:level="1"><nlm:aff id="A3">Laboratorio de Virología Molecular, Centro de Microbiología y Biología Celular, Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela</nlm:aff><country xml:lang="fr">Venezuela</country><wicri:regionArea>Laboratorio de Virología Molecular, Centro de Microbiología y Biología Celular, Instituto Venezolano de Investigaciones Científicas, Caracas</wicri:regionArea><wicri:noRegion>Caracas</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmc">7081067</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081067</idno><idno type="RBID">PMC:7081067</idno><idno type="doi">10.17179/excli2020-1189</idno><idno type="pmid">NONE</idno><date when="2020">2020</date><idno type="wicri:Area/Pmc/Corpus">000839</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000839</idno><idno type="wicri:Area/Pmc/Curation">000839</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000839</idno><idno type="wicri:Area/Pmc/Checkpoint">000009</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000009</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Unrevealing sequence and structural features of novel coronavirus using <italic>in silico</italic> approaches: The main protease as molecular target</title><author><name sortKey="Ortega, Joseph Thomas" sort="Ortega, Joseph Thomas" uniqKey="Ortega J" first="Joseph Thomas" last="Ortega">Joseph Thomas Ortega</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Pharmacology and Cleveland Center for Membrane and Structural Biology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pharmacology and Cleveland Center for Membrane and Structural Biology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Serrano, Maria Luisa" sort="Serrano, Maria Luisa" uniqKey="Serrano M" first="Maria Luisa" last="Serrano">Maria Luisa Serrano</name><affiliation wicri:level="1"><nlm:aff id="A2">Unidad de Química Medicinal, Facultad de Farmacia, Universidad Central de Venezuela, Caracas, Venezuela</nlm:aff><country xml:lang="fr">Venezuela</country><wicri:regionArea>Unidad de Química Medicinal, Facultad de Farmacia, Universidad Central de Venezuela, Caracas</wicri:regionArea><wicri:noRegion>Caracas</wicri:noRegion></affiliation></author><author><name sortKey="Pujol, Flor Helene" sort="Pujol, Flor Helene" uniqKey="Pujol F" first="Flor Helene" last="Pujol">Flor Helene Pujol</name><affiliation wicri:level="1"><nlm:aff id="A3">Laboratorio de Virología Molecular, Centro de Microbiología y Biología Celular, Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela</nlm:aff><country xml:lang="fr">Venezuela</country><wicri:regionArea>Laboratorio de Virología Molecular, Centro de Microbiología y Biología Celular, Instituto Venezolano de Investigaciones Científicas, Caracas</wicri:regionArea><wicri:noRegion>Caracas</wicri:noRegion></affiliation></author><author><name sortKey="Rangel, Hector Rafael" sort="Rangel, Hector Rafael" uniqKey="Rangel H" first="Hector Rafael" last="Rangel">Hector Rafael Rangel</name><affiliation wicri:level="1"><nlm:aff id="A3">Laboratorio de Virología Molecular, Centro de Microbiología y Biología Celular, Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela</nlm:aff><country xml:lang="fr">Venezuela</country><wicri:regionArea>Laboratorio de Virología Molecular, Centro de Microbiología y Biología Celular, Instituto Venezolano de Investigaciones Científicas, Caracas</wicri:regionArea><wicri:noRegion>Caracas</wicri:noRegion></affiliation></author></analytic><series><title level="j">EXCLI Journal</title><idno type="eISSN">1611-2156</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Direct-acting antivirals are effective tools to control viral infections. SARS-CoV-2 is a coronavirus associated with the epidemiological outbreak in late 2019. Previous reports showed that HIV-1 protease inhibitors could block SARS-CoV main protease. Based on that and using an <italic>in silico</italic> approach, we evaluated SARS-CoV-2 main protease as a target for HIV-1 protease inhibitors to reveal the structural features related to their antiviral effect. Our results showed that several HIV inhibitors such as lopinavir, ritonavir, and saquinavir produce strong interaction with the active site of SARS-CoV-2 main protease. Furthermore, broad library protease inhibitors obtained from PubChem and ZINC (<ext-link ext-link-type="uri" xlink:href="www.zinc.docking.org">www.zinc.docking.org</ext-link>) were evaluated. Our analysis revealed 20 compounds that could be clustered into three groups based on their chemical features. Then, these structures could serve as leading compounds to develop a series of derivatives optimizing their activity against SARS-CoV-2 and other coronaviruses. Altogether, the results presented in this work contribute to gain a deep understanding of the molecular pharmacology of SARS-CoV-2 treatment and validate the use of protease inhibitors against SARS-CoV-2.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="De Wilde, Ah" uniqKey="De Wilde A">AH de Wilde</name></author><author><name sortKey="Jochmans, D" uniqKey="Jochmans D">D Jochmans</name></author><author><name sortKey="Posthuma, Cc" uniqKey="Posthuma C">CC Posthuma</name></author><author><name sortKey="Zevenhoven Dobbe, Jc" uniqKey="Zevenhoven Dobbe J">JC Zevenhoven-Dobbe</name></author><author><name sortKey="Van Nieuwkoop, S" uniqKey="Van Nieuwkoop S">S van Nieuwkoop</name></author><author><name sortKey="Bestebroer, Tm" uniqKey="Bestebroer T">TM Bestebroer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Wit, E" uniqKey="De Wit E">E de Wit</name></author><author><name sortKey="Feldmann, F" 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<front><journal-meta><journal-id journal-id-type="nlm-ta">EXCLI J</journal-id><journal-id journal-id-type="iso-abbrev">EXCLI J</journal-id><journal-id journal-id-type="publisher-id">EXCLI J</journal-id><journal-title-group><journal-title>EXCLI Journal</journal-title></journal-title-group><issn pub-type="epub">1611-2156</issn><publisher><publisher-name>Leibniz Research Centre for Working Environment and Human Factors</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmc">7081067</article-id><article-id pub-id-type="publisher-id">2020-1189</article-id><article-id pub-id-type="doi">10.17179/excli2020-1189</article-id><article-id pub-id-type="publisher-id">Doc400</article-id><article-categories><subj-group subj-group-type="heading"><subject>Original Article</subject></subj-group></article-categories><title-group><article-title>Unrevealing sequence and structural features of novel coronavirus using <italic>in silico</italic> approaches: The main protease as molecular target</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Ortega</surname><given-names>Joseph Thomas</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Serrano</surname><given-names>Maria Luisa</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Pujol</surname><given-names>Flor Helene</given-names></name><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Rangel</surname><given-names>Hector Rafael</given-names></name><xref ref-type="corresp" rid="COR1">*</xref><xref ref-type="aff" rid="A3">3</xref></contrib></contrib-group><aff id="A1"><label>1</label>Department of Pharmacology and Cleveland Center for Membrane and Structural Biology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA</aff><aff id="A2"><label>2</label>Unidad de Química Medicinal, Facultad de Farmacia, Universidad Central de Venezuela, Caracas, Venezuela</aff><aff id="A3"><label>3</label>Laboratorio de Virología Molecular, Centro de Microbiología y Biología Celular, Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela</aff><author-notes><corresp id="COR1">*To whom correspondence should be addressed: Hector Rafael Rangel, Laboratorio de Virología Molecular, Centro de Microbiología y Biología Celular, Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela, E-mail: <email>hrangel2006@gmail.com</email></corresp></author-notes><pub-date pub-type="epub"><day>17</day><month>3</month><year>2020</year></pub-date><pub-date pub-type="collection"><year>2020</year></pub-date><volume>19</volume><fpage>400</fpage><lpage>409</lpage><history><date date-type="received"><day>04</day><month>3</month><year>2020</year></date><date date-type="accepted"><day>16</day><month>3</month><year>2020</year></date></history><permissions><copyright-statement>Copyright © 2020 Ortega et al.</copyright-statement><copyright-year>2020</copyright-year><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p><pmc-comment>CREATIVE COMMONS</pmc-comment>This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>) You are free to copy, distribute and transmit the work, provided the original author and source are credited.</license-p></license></permissions><self-uri xlink:type="simple" xlink:href="https://www.excli.de/vol19/Rangel_17032020_proof.pdf">This article is available from https://www.excli.de/vol19/Rangel_17032020_proof.pdf</self-uri><abstract><p>Direct-acting antivirals are effective tools to control viral infections. SARS-CoV-2 is a coronavirus associated with the epidemiological outbreak in late 2019. Previous reports showed that HIV-1 protease inhibitors could block SARS-CoV main protease. Based on that and using an <italic>in silico</italic> approach, we evaluated SARS-CoV-2 main protease as a target for HIV-1 protease inhibitors to reveal the structural features related to their antiviral effect. Our results showed that several HIV inhibitors such as lopinavir, ritonavir, and saquinavir produce strong interaction with the active site of SARS-CoV-2 main protease. Furthermore, broad library protease inhibitors obtained from PubChem and ZINC (<ext-link ext-link-type="uri" xlink:href="www.zinc.docking.org">www.zinc.docking.org</ext-link>) were evaluated. Our analysis revealed 20 compounds that could be clustered into three groups based on their chemical features. Then, these structures could serve as leading compounds to develop a series of derivatives optimizing their activity against SARS-CoV-2 and other coronaviruses. Altogether, the results presented in this work contribute to gain a deep understanding of the molecular pharmacology of SARS-CoV-2 treatment and validate the use of protease inhibitors against SARS-CoV-2.</p></abstract><kwd-group><kwd>Coronavirus</kwd><kwd>SARS-CoV-2</kwd><kwd>protease</kwd><kwd>treatment</kwd><kwd>HIV</kwd></kwd-group></article-meta></front><floats-group><fig id="T1" position="float"><label>Table 1</label><caption><title>Molecular docking of Protease inhibitors used against HIV-1 over SARS-CoVs main proteases</title></caption><graphic xlink:href="EXCLI-19-400-t-001"></graphic></fig><fig id="T2" position="float"><label>Table 2</label><caption><title>Binding energy (BE) values of the best 20 compounds selected as potential inhibitors of SARS-CoV-2 protease. Compound structures were obtained from ZINC database (Bold) and PubChem (italics), lowest BE compound of each group are shown in red.</title></caption><graphic xlink:href="EXCLI-19-400-t-002"></graphic></fig><fig id="F1" position="float"><label>Figure 1</label><caption><title>Phylogenetic analysis of SARS-CoV-2 and other coronaviruses main protease protein. Phylogenetic tree constructed with Poisson correction and 100 bootstrap replicas. The sequences are named with their accession number. The percent homology with SARS-CoV-2 protease protein is shown for some proteins.</title></caption><graphic xlink:href="EXCLI-19-400-g-001"></graphic></fig><fig id="F2" position="float"><label>Figure 2</label><caption><title>Coronavirus main proteases. Graphical representation for each protease was achieved in Biovia Discovery Studio Visualizer by using the coordinates obtained from the Protein Data Bank. Structure for A) Bat-CoV (2YNB), B) SARS-CoV (2GX4), C) SARS-CoV-2 (6LU7) are shown. Also, a comparison by molecular overlapping between these structures is shown in D. The main residues and changes in SARS-CoV-2 compared to SARS-CoV are shown in E. The HIV-1 protease (1MIU) is shown in F.</title></caption><graphic xlink:href="EXCLI-19-400-g-002"></graphic></fig><fig id="F3" position="float"><label>Figure 3</label><caption><title>Coronavirus main proteases. Topological analysis of the catalytic site for SARS-CoV (A) and SARS-CoV-2 (B) main proteases. Conformational residues are highlighted in blue.</title></caption><graphic xlink:href="EXCLI-19-400-g-003"></graphic></fig><fig id="F4" position="float"><label>Figure 4</label><caption><title>Molecular docking of HIV protease inhibitors on SARS-CoV-2 main protease. The molecular docking output represented as lower binding energy frame is shown for each inhibitor. 3D (left) and 2D (right) representations showing the main interaction between the inhibitor and the receptor are displayed. A) Saquinavir, B) Ritonavir, and C) Lopinavir</title></caption><graphic xlink:href="EXCLI-19-400-g-004"></graphic></fig><fig id="F5" position="float"><label>Figure 5</label><caption><title>Hierarchical clustering of the top 20 best protease inhibitors obtained from public libraries (ZINC and PubChem) that could block SARS-CoV-2 protease. The compounds were clustered by chemical structure based in the Tanimoto coefficient where 0: the same structure and 1: no chemical relationship.</title></caption><graphic xlink:href="EXCLI-19-400-g-005"></graphic></fig><fig id="F6" position="float"><label>Figure 6</label><caption><title>Chemical structure and ADME parameters of top five protease inhibitors obtained from public libraries (ZINC and PubChem) that could block SARS-CoV-2 protease. The colored zone is the suitable physicochemical space for oral bioavailability. LIPO (Lipophility): -0.7 </title> </caption><graphic xlink:href="EXCLI-19-400-g-006"></graphic></fig></floats-group></pmc><affiliations><list><country><li>Venezuela</li><li>États-Unis</li></country><region><li>Ohio</li></region></list><tree><country name="États-Unis"><region name="Ohio"><name sortKey="Ortega, Joseph Thomas" sort="Ortega, Joseph Thomas" uniqKey="Ortega J" first="Joseph Thomas" last="Ortega">Joseph Thomas Ortega</name></region></country><country name="Venezuela"><noRegion><name sortKey="Serrano, Maria Luisa" sort="Serrano, Maria Luisa" uniqKey="Serrano M" first="Maria Luisa" last="Serrano">Maria Luisa Serrano</name></noRegion><name sortKey="Pujol, Flor Helene" sort="Pujol, Flor Helene" uniqKey="Pujol F" first="Flor Helene" last="Pujol">Flor Helene Pujol</name><name sortKey="Rangel, Hector Rafael" sort="Rangel, Hector Rafael" uniqKey="Rangel H" first="Hector Rafael" last="Rangel">Hector Rafael Rangel</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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