Silybin B and Cianidanol Inhibit M pro and Spike Protein of SARS-CoV-2: Evidence from in Silico Molecular Docking Studies.
Identifieur interne : 000693 ( Main/Corpus ); précédent : 000692; suivant : 000694Silybin B and Cianidanol Inhibit M pro and Spike Protein of SARS-CoV-2: Evidence from in Silico Molecular Docking Studies.
Auteurs : Rashi Srivastava ; Shubham Tripathi ; Sreepoorna Unni ; Arif Hussain ; Shafiul Haque ; Nandita Dasgupta ; Vineeta Singh ; Bhartendu Nath MishraSource :
- Current pharmaceutical design [ 1873-4286 ] ; 2020.
Abstract
BACKGROUND
The main proteases (Mpro) and Spike Proteins (SP) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARSCoV-2) play a major role in viral infection development by producing several non-structural proteins (nsPs) and penetrating the host cells respectively. In this study, the potential of in silico molecular docking-based drug repositioning approach was exploited for identifying the inhibitors of Mpro and SP of SARS-CoV-2.
METHODS
A total of 196 compounds including various US-FDA-approved drugs, vitamins and their analogs were docked with Mpro (PDB IDs: 6YB7 and 6Y84), and the top six ligands were further tested for ADME properties followed by docking with SP (PDB IDs: 6LXT and 6W41).
RESULTS
Out of 196 compounds, binding energy (DE) of Silybin B (6YB7: DE: -11.20 kcal/mol; 6Y84: DE: -10.18 kcal/mol; 6LXT:DE: -10.47 kcal/mol; 6W41:DE: -10.96 kcal/mol) and Cianidanol (6YB7:DE: -8.85 kcal/mol; 6Y84:DE:-10.02 kcal/mol; 6LXT:DE:-9.36 kcal/mol; 6W41:DE: -9.52 kcal/mol) demonstrated better binding and ADME properties compared with the currently endeavored drugs like Hydroxychloroquine and Lopinavir. Additionally, Elliptinone, Diospyirin, SCHEMBL94263 and Fiboflavin have shown encouraging results. Fiboflavin, an immunity booster, was found to inhibit both the Mpro and spike protein of SARS-CoV-2. It was observed that amino acid residues MET6, ALA7, PHE8, PRO9, ASP295, GLY302, VAL303 and THR304 play significant roles in protein-ligand interactions through hydrogen bonds and Vander Waals forces.
CONCLUSION
Silybin B and Cianidanol showed excellent binding and ADME properties compared with the currently endeavored drugs and can be exploited as therapeutic options against SARS-CoV-2 infection after experimental validation and clinical trials.
DOI: 10.2174/1381612826666201210122726
PubMed: 33302853
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India.</nlm:affiliation></affiliation></author><author><name sortKey="Unni, Sreepoorna" sort="Unni, Sreepoorna" uniqKey="Unni S" first="Sreepoorna" last="Unni">Sreepoorna Unni</name><affiliation><nlm:affiliation>Department of Life and Environmental Sciences, College of Natural & Health, Zayed University, P.O. Box 19282, Dubai. United Arab Emirates.</nlm:affiliation></affiliation></author><author><name sortKey="Hussain, Arif" sort="Hussain, Arif" uniqKey="Hussain A" first="Arif" last="Hussain">Arif Hussain</name><affiliation><nlm:affiliation>School of Life Sciences, Manipal Academy of Higher Education, P.O. Box 345050, Dubai. United Arab Emirates.</nlm:affiliation></affiliation></author><author><name sortKey="Haque, Shafiul" sort="Haque, Shafiul" uniqKey="Haque S" first="Shafiul" last="Haque">Shafiul Haque</name><affiliation><nlm:affiliation>Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan-45142. Saudi Arabia.</nlm:affiliation></affiliation></author><author><name sortKey="Dasgupta, Nandita" sort="Dasgupta, Nandita" uniqKey="Dasgupta N" first="Nandita" last="Dasgupta">Nandita Dasgupta</name><affiliation><nlm:affiliation>Department of Biotechnology, Institute of Engineering and Technology, Dr. A.P.J. Abdul Kalam Technical University, Lucknow-226021, Uttar Pradesh. India.</nlm:affiliation></affiliation></author><author><name sortKey="Singh, Vineeta" sort="Singh, Vineeta" uniqKey="Singh V" first="Vineeta" last="Singh">Vineeta Singh</name><affiliation><nlm:affiliation>Department of Biotechnology, Institute of Engineering and Technology, Dr. A.P.J. Abdul Kalam Technical University, Lucknow-226021, Uttar Pradesh. India.</nlm:affiliation></affiliation></author><author><name sortKey="Mishra, Bhartendu Nath" sort="Mishra, Bhartendu Nath" uniqKey="Mishra B" first="Bhartendu Nath" last="Mishra">Bhartendu Nath Mishra</name><affiliation><nlm:affiliation>Department of Biotechnology, Institute of Engineering and Technology, Dr. A.P.J. Abdul Kalam Technical University, Lucknow-226021, Uttar Pradesh. India.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:33302853</idno><idno type="pmid">33302853</idno><idno type="doi">10.2174/1381612826666201210122726</idno><idno type="wicri:Area/Main/Corpus">000693</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000693</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Silybin B and Cianidanol Inhibit M pro and Spike Protein of SARS-CoV-2: Evidence from in Silico Molecular Docking Studies.</title><author><name sortKey="Srivastava, Rashi" sort="Srivastava, Rashi" uniqKey="Srivastava R" first="Rashi" last="Srivastava">Rashi Srivastava</name><affiliation><nlm:affiliation>Department of Biotechnology, Institute of Engineering and Technology, Dr. A.P.J. Abdul Kalam Technical University, Lucknow-226021, Uttar Pradesh. India.</nlm:affiliation></affiliation></author><author><name sortKey="Tripathi, Shubham" sort="Tripathi, Shubham" uniqKey="Tripathi S" first="Shubham" last="Tripathi">Shubham Tripathi</name><affiliation><nlm:affiliation>Department of Biotechnology, Institute of Engineering and Technology, Dr. A.P.J. Abdul Kalam Technical University, Lucknow-226021, Uttar Pradesh. India.</nlm:affiliation></affiliation></author><author><name sortKey="Unni, Sreepoorna" sort="Unni, Sreepoorna" uniqKey="Unni S" first="Sreepoorna" last="Unni">Sreepoorna Unni</name><affiliation><nlm:affiliation>Department of Life and Environmental Sciences, College of Natural & Health, Zayed University, P.O. Box 19282, Dubai. United Arab Emirates.</nlm:affiliation></affiliation></author><author><name sortKey="Hussain, Arif" sort="Hussain, Arif" uniqKey="Hussain A" first="Arif" last="Hussain">Arif Hussain</name><affiliation><nlm:affiliation>School of Life Sciences, Manipal Academy of Higher Education, P.O. Box 345050, Dubai. United Arab Emirates.</nlm:affiliation></affiliation></author><author><name sortKey="Haque, Shafiul" sort="Haque, Shafiul" uniqKey="Haque S" first="Shafiul" last="Haque">Shafiul Haque</name><affiliation><nlm:affiliation>Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan-45142. Saudi Arabia.</nlm:affiliation></affiliation></author><author><name sortKey="Dasgupta, Nandita" sort="Dasgupta, Nandita" uniqKey="Dasgupta N" first="Nandita" last="Dasgupta">Nandita Dasgupta</name><affiliation><nlm:affiliation>Department of Biotechnology, Institute of Engineering and Technology, Dr. A.P.J. Abdul Kalam Technical University, Lucknow-226021, Uttar Pradesh. India.</nlm:affiliation></affiliation></author><author><name sortKey="Singh, Vineeta" sort="Singh, Vineeta" uniqKey="Singh V" first="Vineeta" last="Singh">Vineeta Singh</name><affiliation><nlm:affiliation>Department of Biotechnology, Institute of Engineering and Technology, Dr. A.P.J. Abdul Kalam Technical University, Lucknow-226021, Uttar Pradesh. India.</nlm:affiliation></affiliation></author><author><name sortKey="Mishra, Bhartendu Nath" sort="Mishra, Bhartendu Nath" uniqKey="Mishra B" first="Bhartendu Nath" last="Mishra">Bhartendu Nath Mishra</name><affiliation><nlm:affiliation>Department of Biotechnology, Institute of Engineering and Technology, Dr. A.P.J. Abdul Kalam Technical University, Lucknow-226021, Uttar Pradesh. India.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Current pharmaceutical design</title><idno type="eISSN">1873-4286</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><b>BACKGROUND</b></p><p>The main proteases (Mpro) and Spike Proteins (SP) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARSCoV-2) play a major role in viral infection development by producing several non-structural proteins (nsPs) and penetrating the host cells respectively. In this study, the potential of in silico molecular docking-based drug repositioning approach was exploited for identifying the inhibitors of Mpro and SP of SARS-CoV-2.</p></div><div type="abstract" xml:lang="en"><p><b>METHODS</b></p><p>A total of 196 compounds including various US-FDA-approved drugs, vitamins and their analogs were docked with Mpro (PDB IDs: 6YB7 and 6Y84), and the top six ligands were further tested for ADME properties followed by docking with SP (PDB IDs: 6LXT and 6W41).</p></div><div type="abstract" xml:lang="en"><p><b>RESULTS</b></p><p>Out of 196 compounds, binding energy (DE) of Silybin B (6YB7: DE: -11.20 kcal/mol; 6Y84: DE: -10.18 kcal/mol; 6LXT:DE: -10.47 kcal/mol; 6W41:DE: -10.96 kcal/mol) and Cianidanol (6YB7:DE: -8.85 kcal/mol; 6Y84:DE:-10.02 kcal/mol; 6LXT:DE:-9.36 kcal/mol; 6W41:DE: -9.52 kcal/mol) demonstrated better binding and ADME properties compared with the currently endeavored drugs like Hydroxychloroquine and Lopinavir. Additionally, Elliptinone, Diospyirin, SCHEMBL94263 and Fiboflavin have shown encouraging results. Fiboflavin, an immunity booster, was found to inhibit both the Mpro and spike protein of SARS-CoV-2. It was observed that amino acid residues MET6, ALA7, PHE8, PRO9, ASP295, GLY302, VAL303 and THR304 play significant roles in protein-ligand interactions through hydrogen bonds and Vander Waals forces.</p></div><div type="abstract" xml:lang="en"><p><b>CONCLUSION</b></p><p>Silybin B and Cianidanol showed excellent binding and ADME properties compared with the currently endeavored drugs and can be exploited as therapeutic options against SARS-CoV-2 infection after experimental validation and clinical trials.</p></div></front></TEI><pubmed><MedlineCitation Status="Publisher" Owner="NLM"><PMID Version="1">33302853</PMID><DateRevised><Year>2020</Year><Month>12</Month><Day>11</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1873-4286</ISSN><JournalIssue CitedMedium="Internet"><PubDate><Year>2020</Year><Month>Dec</Month><Day>10</Day></PubDate></JournalIssue><Title>Current pharmaceutical design</Title><ISOAbbreviation>Curr Pharm Des</ISOAbbreviation></Journal><ArticleTitle>Silybin B and Cianidanol Inhibit M pro and Spike Protein of SARS-CoV-2: Evidence from in Silico Molecular Docking Studies.</ArticleTitle><ELocationID EIdType="doi" ValidYN="Y">10.2174/1381612826666201210122726</ELocationID><Abstract><AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">The main proteases (Mpro) and Spike Proteins (SP) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARSCoV-2) play a major role in viral infection development by producing several non-structural proteins (nsPs) and penetrating the host cells respectively. In this study, the potential of in silico molecular docking-based drug repositioning approach was exploited for identifying the inhibitors of Mpro and SP of SARS-CoV-2.</AbstractText><AbstractText Label="METHODS" NlmCategory="METHODS">A total of 196 compounds including various US-FDA-approved drugs, vitamins and their analogs were docked with Mpro (PDB IDs: 6YB7 and 6Y84), and the top six ligands were further tested for ADME properties followed by docking with SP (PDB IDs: 6LXT and 6W41).</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">Out of 196 compounds, binding energy (DE) of Silybin B (6YB7: DE: -11.20 kcal/mol; 6Y84: DE: -10.18 kcal/mol; 6LXT:DE: -10.47 kcal/mol; 6W41:DE: -10.96 kcal/mol) and Cianidanol (6YB7:DE: -8.85 kcal/mol; 6Y84:DE:-10.02 kcal/mol; 6LXT:DE:-9.36 kcal/mol; 6W41:DE: -9.52 kcal/mol) demonstrated better binding and ADME properties compared with the currently endeavored drugs like Hydroxychloroquine and Lopinavir. Additionally, Elliptinone, Diospyirin, SCHEMBL94263 and Fiboflavin have shown encouraging results. Fiboflavin, an immunity booster, was found to inhibit both the Mpro and spike protein of SARS-CoV-2. It was observed that amino acid residues MET6, ALA7, PHE8, PRO9, ASP295, GLY302, VAL303 and THR304 play significant roles in protein-ligand interactions through hydrogen bonds and Vander Waals forces.</AbstractText><AbstractText Label="CONCLUSION" NlmCategory="CONCLUSIONS">Silybin B and Cianidanol showed excellent binding and ADME properties compared with the currently endeavored drugs and can be exploited as therapeutic options against SARS-CoV-2 infection after experimental validation and clinical trials.</AbstractText><CopyrightInformation>Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Srivastava</LastName><ForeName>Rashi</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Department of Biotechnology, Institute of Engineering and Technology, Dr. A.P.J. Abdul Kalam Technical University, Lucknow-226021, Uttar Pradesh. India.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tripathi</LastName><ForeName>Shubham</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Biotechnology, Institute of Engineering and Technology, Dr. A.P.J. Abdul Kalam Technical University, Lucknow-226021, Uttar Pradesh. India.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Unni</LastName><ForeName>Sreepoorna</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Life and Environmental Sciences, College of Natural & Health, Zayed University, P.O. Box 19282, Dubai. United Arab Emirates.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hussain</LastName><ForeName>Arif</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>School of Life Sciences, Manipal Academy of Higher Education, P.O. Box 345050, Dubai. United Arab Emirates.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Haque</LastName><ForeName>Shafiul</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan-45142. Saudi Arabia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dasgupta</LastName><ForeName>Nandita</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Department of Biotechnology, Institute of Engineering and Technology, Dr. A.P.J. Abdul Kalam Technical University, Lucknow-226021, Uttar Pradesh. India.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Singh</LastName><ForeName>Vineeta</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>Department of Biotechnology, Institute of Engineering and Technology, Dr. A.P.J. Abdul Kalam Technical University, Lucknow-226021, Uttar Pradesh. India.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mishra</LastName><ForeName>Bhartendu Nath</ForeName><Initials>BN</Initials><AffiliationInfo><Affiliation>Department of Biotechnology, Institute of Engineering and Technology, Dr. A.P.J. Abdul Kalam Technical University, Lucknow-226021, Uttar Pradesh. India.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>12</Month><Day>10</Day></ArticleDate></Article><MedlineJournalInfo><Country>United Arab Emirates</Country><MedlineTA>Curr Pharm Des</MedlineTA><NlmUniqueID>9602487</NlmUniqueID><ISSNLinking>1381-6128</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">COVID-19</Keyword><Keyword MajorTopicYN="N">Cianidanol</Keyword><Keyword MajorTopicYN="N">Fiboflavin</Keyword><Keyword MajorTopicYN="N">Mpro</Keyword><Keyword MajorTopicYN="N">SARS-CoV-2</Keyword><Keyword MajorTopicYN="N">Silybin B</Keyword><Keyword MajorTopicYN="N">Spike Protein</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year><Month>08</Month><Day>02</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2020</Year><Month>10</Month><Day>07</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2020</Year><Month>10</Month><Day>14</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>12</Month><Day>11</Day><Hour>5</Hour><Minute>34</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>12</Month><Day>12</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>12</Month><Day>12</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>aheadofprint</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">33302853</ArticleId><ArticleId IdType="pii">CPD-EPUB-112296</ArticleId><ArticleId IdType="doi">10.2174/1381612826666201210122726</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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