Potential inhibitors for the novel coronavirus (SARS-CoV-2).
Identifieur interne : 000C03 ( Main/Corpus ); précédent : 000C02; suivant : 000C04Potential inhibitors for the novel coronavirus (SARS-CoV-2).
Auteurs : Yanqiang Han ; Zhilong Wang ; Jiahao Ren ; Zhiyun Wei ; Jinjin LiSource :
- Briefings in bioinformatics [ 1477-4054 ] ; 2021.
English descriptors
- KwdEn :
- MESH :
- chemical , chemistry : Antiviral Agents.
- chemical , metabolism : Viral Proteins.
- chemical , pharmacology : Antiviral Agents.
- drug effects : SARS-CoV-2.
- metabolism : SARS-CoV-2.
- virology : COVID-19.
- Drug Design, Humans, Ligands, Molecular Docking Simulation, Thermodynamics.
Abstract
The lack of a vaccine or any effective treatment for the aggressive novel coronavirus disease (COVID-19) has created a sense of urgency for the discovery of effective drugs. Several repurposing pharmaceutical candidates have been reported or envisaged to inhibit the emerging infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but their binding sites, binding affinities and inhibitory mechanisms are still unavailable. In this study, we use the ligand-protein docking program and molecular dynamic simulation to ab initio investigate the binding mechanism and inhibitory ability of seven clinically approved drugs (Chloroquine, Hydroxychloroquine, Remdesivir, Ritonavir, Beclabuvir, Indinavir and Favipiravir) and a recently designed α-ketoamide inhibitor (13b) at the molecular level. The results suggest that Chloroquine has the strongest binding affinity with 3CL hydrolase (Mpro) among clinically approved drugs, indicating its effective inhibitory ability for SARS-CoV-2. However, the newly designed inhibitor 13b shows potentially improved inhibition efficiency with larger binding energy compared with Chloroquine. We further calculate the important binding site residues at the active site and demonstrate that the MET 165 and HIE 163 contribute the most for 13b, while the MET 165 and GLN 189 for Chloroquine, based on residual energy decomposition analysis. The proposed work offers a higher research priority for 13b to treat the infection of SARS-CoV-2 and provides theoretical basis for further design of effective drug molecules with stronger inhibition.
DOI: 10.1093/bib/bbaa209
PubMed: 32942296
PubMed Central: PMC7543260
Links to Exploration step
pubmed:32942296Le document en format XML
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Key Laboratory for Thin Film and Microfabrication of Ministry of Education, Department of Micro/Nano Electronics, Shanghai Jiao Tong University.</nlm:affiliation></affiliation></author><author><name sortKey="Li, Jinjin" sort="Li, Jinjin" uniqKey="Li J" first="Jinjin" last="Li">Jinjin Li</name><affiliation><nlm:affiliation>National Key Laboratory of Science and Technology on Micro/Nano Fabrication, Shanghai Jiao Tong University, Shanghai, 200240, China.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2021">2021</date><idno type="RBID">pubmed:32942296</idno><idno type="pmid">32942296</idno><idno type="doi">10.1093/bib/bbaa209</idno><idno type="pmc">PMC7543260</idno><idno type="wicri:Area/Main/Corpus">000C03</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000C03</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Potential inhibitors for the novel coronavirus (SARS-CoV-2).</title><author><name sortKey="Han, Yanqiang" sort="Han, Yanqiang" uniqKey="Han Y" first="Yanqiang" last="Han">Yanqiang Han</name><affiliation><nlm:affiliation>Shanghai Jiao Tong University.</nlm:affiliation></affiliation></author><author><name sortKey="Wang, Zhilong" sort="Wang, Zhilong" uniqKey="Wang Z" first="Zhilong" last="Wang">Zhilong Wang</name><affiliation><nlm:affiliation>Shanghai Jiao Tong University.</nlm:affiliation></affiliation></author><author><name sortKey="Ren, Jiahao" sort="Ren, Jiahao" uniqKey="Ren J" first="Jiahao" last="Ren">Jiahao Ren</name><affiliation><nlm:affiliation>Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine.</nlm:affiliation></affiliation></author><author><name sortKey="Wei, Zhiyun" sort="Wei, Zhiyun" uniqKey="Wei Z" first="Zhiyun" last="Wei">Zhiyun Wei</name><affiliation><nlm:affiliation>National Key Laboratory of Science and Technology on Micro/Nano Fabrication; Key Laboratory for Thin Film and Microfabrication of Ministry of Education, Department of Micro/Nano Electronics, Shanghai Jiao Tong University.</nlm:affiliation></affiliation></author><author><name sortKey="Li, Jinjin" sort="Li, Jinjin" uniqKey="Li J" first="Jinjin" last="Li">Jinjin Li</name><affiliation><nlm:affiliation>National Key Laboratory of Science and Technology on Micro/Nano Fabrication, Shanghai Jiao Tong University, Shanghai, 200240, China.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Briefings in bioinformatics</title><idno type="eISSN">1477-4054</idno><imprint><date when="2021" type="published">2021</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antiviral Agents (chemistry)</term><term>Antiviral Agents (pharmacology)</term><term>COVID-19 (virology)</term><term>Drug Design (MeSH)</term><term>Humans (MeSH)</term><term>Ligands (MeSH)</term><term>Molecular Docking Simulation (MeSH)</term><term>SARS-CoV-2 (drug effects)</term><term>SARS-CoV-2 (metabolism)</term><term>Thermodynamics (MeSH)</term><term>Viral Proteins (metabolism)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Antiviral Agents</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Viral Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antiviral Agents</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>SARS-CoV-2</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>SARS-CoV-2</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>COVID-19</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Drug Design</term><term>Humans</term><term>Ligands</term><term>Molecular Docking Simulation</term><term>Thermodynamics</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The lack of a vaccine or any effective treatment for the aggressive novel coronavirus disease (COVID-19) has created a sense of urgency for the discovery of effective drugs. Several repurposing pharmaceutical candidates have been reported or envisaged to inhibit the emerging infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but their binding sites, binding affinities and inhibitory mechanisms are still unavailable. In this study, we use the ligand-protein docking program and molecular dynamic simulation to ab initio investigate the binding mechanism and inhibitory ability of seven clinically approved drugs (Chloroquine, Hydroxychloroquine, Remdesivir, Ritonavir, Beclabuvir, Indinavir and Favipiravir) and a recently designed α-ketoamide inhibitor (13b) at the molecular level. The results suggest that Chloroquine has the strongest binding affinity with 3CL hydrolase (Mpro) among clinically approved drugs, indicating its effective inhibitory ability for SARS-CoV-2. However, the newly designed inhibitor 13b shows potentially improved inhibition efficiency with larger binding energy compared with Chloroquine. We further calculate the important binding site residues at the active site and demonstrate that the MET 165 and HIE 163 contribute the most for 13b, while the MET 165 and GLN 189 for Chloroquine, based on residual energy decomposition analysis. The proposed work offers a higher research priority for 13b to treat the infection of SARS-CoV-2 and provides theoretical basis for further design of effective drug molecules with stronger inhibition.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">32942296</PMID><DateCompleted><Year>2021</Year><Month>04</Month><Day>14</Day></DateCompleted><DateRevised><Year>2021</Year><Month>04</Month><Day>14</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1477-4054</ISSN><JournalIssue CitedMedium="Internet"><Volume>22</Volume><Issue>2</Issue><PubDate><Year>2021</Year><Month>03</Month><Day>22</Day></PubDate></JournalIssue><Title>Briefings in bioinformatics</Title><ISOAbbreviation>Brief Bioinform</ISOAbbreviation></Journal><ArticleTitle>Potential inhibitors for the novel coronavirus (SARS-CoV-2).</ArticleTitle><Pagination><MedlinePgn>1225-1231</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1093/bib/bbaa209</ELocationID><Abstract><AbstractText>The lack of a vaccine or any effective treatment for the aggressive novel coronavirus disease (COVID-19) has created a sense of urgency for the discovery of effective drugs. Several repurposing pharmaceutical candidates have been reported or envisaged to inhibit the emerging infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but their binding sites, binding affinities and inhibitory mechanisms are still unavailable. In this study, we use the ligand-protein docking program and molecular dynamic simulation to ab initio investigate the binding mechanism and inhibitory ability of seven clinically approved drugs (Chloroquine, Hydroxychloroquine, Remdesivir, Ritonavir, Beclabuvir, Indinavir and Favipiravir) and a recently designed α-ketoamide inhibitor (13b) at the molecular level. The results suggest that Chloroquine has the strongest binding affinity with 3CL hydrolase (Mpro) among clinically approved drugs, indicating its effective inhibitory ability for SARS-CoV-2. However, the newly designed inhibitor 13b shows potentially improved inhibition efficiency with larger binding energy compared with Chloroquine. We further calculate the important binding site residues at the active site and demonstrate that the MET 165 and HIE 163 contribute the most for 13b, while the MET 165 and GLN 189 for Chloroquine, based on residual energy decomposition analysis. The proposed work offers a higher research priority for 13b to treat the infection of SARS-CoV-2 and provides theoretical basis for further design of effective drug molecules with stronger inhibition.</AbstractText><CopyrightInformation>© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Han</LastName><ForeName>Yanqiang</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Shanghai Jiao Tong University.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Zhilong</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>Shanghai Jiao Tong University.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ren</LastName><ForeName>Jiahao</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wei</LastName><ForeName>Zhiyun</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>National Key Laboratory of Science and Technology on Micro/Nano Fabrication; Key Laboratory for Thin Film and Microfabrication of Ministry of Education, Department of Micro/Nano Electronics, Shanghai Jiao Tong University.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Jinjin</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>National Key Laboratory of Science and Technology on Micro/Nano Fabrication, Shanghai Jiao Tong University, Shanghai, 200240, China.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Brief Bioinform</MedlineTA><NlmUniqueID>100912837</NlmUniqueID><ISSNLinking>1467-5463</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000998">Antiviral Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D008024">Ligands</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D014764">Viral Proteins</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000998" MajorTopicYN="N">Antiviral Agents</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000086382" MajorTopicYN="N">COVID-19</DescriptorName><QualifierName UI="Q000821" MajorTopicYN="Y">virology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015195" MajorTopicYN="N">Drug Design</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008024" MajorTopicYN="N">Ligands</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D062105" MajorTopicYN="N">Molecular Docking Simulation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000086402" MajorTopicYN="N">SARS-CoV-2</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D013816" MajorTopicYN="N">Thermodynamics</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014764" MajorTopicYN="N">Viral Proteins</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">3CL Mpro</Keyword><Keyword MajorTopicYN="Y">COVID-19</Keyword><Keyword MajorTopicYN="Y">SARS-CoV-2</Keyword><Keyword MajorTopicYN="Y">binding free energy</Keyword><Keyword MajorTopicYN="Y">drug design</Keyword><Keyword MajorTopicYN="Y">ligand-protein docking</Keyword><Keyword MajorTopicYN="Y">α-ketoamide inhibitor</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year><Month>04</Month><Day>29</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2020</Year><Month>07</Month><Day>27</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2020</Year><Month>08</Month><Day>12</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>9</Month><Day>18</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2021</Year><Month>4</Month><Day>15</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>9</Month><Day>17</Day><Hour>20</Hour><Minute>24</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">32942296</ArticleId><ArticleId IdType="pii">5907953</ArticleId><ArticleId IdType="doi">10.1093/bib/bbaa209</ArticleId><ArticleId IdType="pmc">PMC7543260</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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