Transcriptomic signatures and repurposing drugs for COVID-19 patients: findings of bioinformatics analyses.
Identifieur interne : 000676 ( Main/Corpus ); précédent : 000675; suivant : 000677Transcriptomic signatures and repurposing drugs for COVID-19 patients: findings of bioinformatics analyses.
Auteurs : Guobing Li ; Shasha Ruan ; Xiaolu Zhao ; Qi Liu ; Yali Dou ; Fengbiao MaoSource :
- Computational and structural biotechnology journal [ 2001-0370 ] ; 2021.
Abstract
The novel coronavirus SARS-CoV-2 is damaging the world's social and economic fabrics seriously. Effective drugs are urgently needed to decrease the high mortality rate of COVID-19 patients. Unfortunately, effective antiviral drugs or vaccines are currently unavailable. Herein, we systematically evaluated the effect of SARS-CoV-2 on gene expression of both lung tissue and blood from COVID-19 patients using transcriptome profiling. Differential gene expression analysis revealed potential core mechanism of COVID-19-induced pneumonia in which IFN-α, IFN-β, IFN-γ, TNF and IL6 triggered cytokine storm mediated by neutrophil, macrophage, B and DC cells. Weighted gene correlation network analysis identified two gene modules that are highly correlated with clinical traits of COVID-19 patients, and confirmed that over-activation of immune system-mediated cytokine release syndrome is the underlying pathogenic mechanism for acute phase of COVID-19 infection. It suggested that anti-inflammatory therapies may be promising regimens for COVID-19 patients. Furthermore, drug repurposing analysis of thousands of drugs revealed that TNFα inhibitor etanercept and γ-aminobutyric acid-B receptor (GABABR) agonist baclofen showed most significant reversal power to COVID-19 gene signature, so we are highly optimistic about their clinical use for COVID-19 treatment. In addition, our results suggested that adalimumab, tocilizumab, rituximab and glucocorticoids may also have beneficial effects in restoring normal transcriptome, but not chloroquine, hydroxychloroquine or interferons. Controlled clinical trials of these candidate drugs are needed in search of effective COVID-19 treatment in current crisis.
DOI: 10.1016/j.csbj.2020.11.056
PubMed: 33312453
PubMed Central: PMC7719282
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Hubei 430060, China.</nlm:affiliation></affiliation></author><author><name sortKey="Zhao, Xiaolu" sort="Zhao, Xiaolu" uniqKey="Zhao X" first="Xiaolu" last="Zhao">Xiaolu Zhao</name><affiliation><nlm:affiliation>Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China.</nlm:affiliation></affiliation></author><author><name sortKey="Liu, Qi" sort="Liu, Qi" uniqKey="Liu Q" first="Qi" last="Liu">Qi Liu</name><affiliation><nlm:affiliation>Stem Cell Program, Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, USA.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Dou, Yali" sort="Dou, Yali" uniqKey="Dou Y" first="Yali" last="Dou">Yali Dou</name><affiliation><nlm:affiliation>Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Mao, Fengbiao" sort="Mao, Fengbiao" uniqKey="Mao F" first="Fengbiao" last="Mao">Fengbiao Mao</name><affiliation><nlm:affiliation>Center of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing 100191, China.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2021">2021</date><idno type="RBID">pubmed:33312453</idno><idno type="pmid">33312453</idno><idno type="doi">10.1016/j.csbj.2020.11.056</idno><idno type="pmc">PMC7719282</idno><idno type="wicri:Area/Main/Corpus">000676</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000676</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Transcriptomic signatures and repurposing drugs for COVID-19 patients: findings of bioinformatics analyses.</title><author><name sortKey="Li, Guobing" sort="Li, Guobing" uniqKey="Li G" first="Guobing" last="Li">Guobing Li</name><affiliation><nlm:affiliation>Center of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing 100191, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Ruan, Shasha" sort="Ruan, Shasha" uniqKey="Ruan S" first="Shasha" last="Ruan">Shasha Ruan</name><affiliation><nlm:affiliation>Department of Clinical Oncology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>The First Clinical College of Wuhan University, Wuhan, Hubei 430060, China.</nlm:affiliation></affiliation></author><author><name sortKey="Zhao, Xiaolu" sort="Zhao, Xiaolu" uniqKey="Zhao X" first="Xiaolu" last="Zhao">Xiaolu Zhao</name><affiliation><nlm:affiliation>Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China.</nlm:affiliation></affiliation></author><author><name sortKey="Liu, Qi" sort="Liu, Qi" uniqKey="Liu Q" first="Qi" last="Liu">Qi Liu</name><affiliation><nlm:affiliation>Stem Cell Program, Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, USA.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Dou, Yali" sort="Dou, Yali" uniqKey="Dou Y" first="Yali" last="Dou">Yali Dou</name><affiliation><nlm:affiliation>Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Mao, Fengbiao" sort="Mao, Fengbiao" uniqKey="Mao F" first="Fengbiao" last="Mao">Fengbiao Mao</name><affiliation><nlm:affiliation>Center of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing 100191, China.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Computational and structural biotechnology journal</title><idno type="ISSN">2001-0370</idno><imprint><date when="2021" type="published">2021</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The novel coronavirus SARS-CoV-2 is damaging the world's social and economic fabrics seriously. Effective drugs are urgently needed to decrease the high mortality rate of COVID-19 patients. Unfortunately, effective antiviral drugs or vaccines are currently unavailable. Herein, we systematically evaluated the effect of SARS-CoV-2 on gene expression of both lung tissue and blood from COVID-19 patients using transcriptome profiling. Differential gene expression analysis revealed potential core mechanism of COVID-19-induced pneumonia in which IFN-α, IFN-β, IFN-γ, TNF and IL6 triggered cytokine storm mediated by neutrophil, macrophage, B and DC cells. Weighted gene correlation network analysis identified two gene modules that are highly correlated with clinical traits of COVID-19 patients, and confirmed that over-activation of immune system-mediated cytokine release syndrome is the underlying pathogenic mechanism for acute phase of COVID-19 infection. It suggested that anti-inflammatory therapies may be promising regimens for COVID-19 patients. Furthermore, drug repurposing analysis of thousands of drugs revealed that TNFα inhibitor etanercept and γ-aminobutyric acid-B receptor (GABABR) agonist baclofen showed most significant reversal power to COVID-19 gene signature, so we are highly optimistic about their clinical use for COVID-19 treatment. In addition, our results suggested that adalimumab, tocilizumab, rituximab and glucocorticoids may also have beneficial effects in restoring normal transcriptome, but not chloroquine, hydroxychloroquine or interferons. Controlled clinical trials of these candidate drugs are needed in search of effective COVID-19 treatment in current crisis.</div></front></TEI><pubmed><MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM"><PMID Version="1">33312453</PMID><DateRevised><Year>2021</Year><Month>01</Month><Day>10</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Print">2001-0370</ISSN><JournalIssue CitedMedium="Print"><Volume>19</Volume><PubDate><Year>2021</Year></PubDate></JournalIssue><Title>Computational and structural biotechnology journal</Title><ISOAbbreviation>Comput Struct Biotechnol J</ISOAbbreviation></Journal><ArticleTitle>Transcriptomic signatures and repurposing drugs for COVID-19 patients: findings of bioinformatics analyses.</ArticleTitle><Pagination><MedlinePgn>1-15</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.csbj.2020.11.056</ELocationID><Abstract><AbstractText>The novel coronavirus SARS-CoV-2 is damaging the world's social and economic fabrics seriously. Effective drugs are urgently needed to decrease the high mortality rate of COVID-19 patients. Unfortunately, effective antiviral drugs or vaccines are currently unavailable. Herein, we systematically evaluated the effect of SARS-CoV-2 on gene expression of both lung tissue and blood from COVID-19 patients using transcriptome profiling. Differential gene expression analysis revealed potential core mechanism of COVID-19-induced pneumonia in which IFN-α, IFN-β, IFN-γ, TNF and IL6 triggered cytokine storm mediated by neutrophil, macrophage, B and DC cells. Weighted gene correlation network analysis identified two gene modules that are highly correlated with clinical traits of COVID-19 patients, and confirmed that over-activation of immune system-mediated cytokine release syndrome is the underlying pathogenic mechanism for acute phase of COVID-19 infection. It suggested that anti-inflammatory therapies may be promising regimens for COVID-19 patients. Furthermore, drug repurposing analysis of thousands of drugs revealed that TNFα inhibitor etanercept and γ-aminobutyric acid-B receptor (GABABR) agonist baclofen showed most significant reversal power to COVID-19 gene signature, so we are highly optimistic about their clinical use for COVID-19 treatment. In addition, our results suggested that adalimumab, tocilizumab, rituximab and glucocorticoids may also have beneficial effects in restoring normal transcriptome, but not chloroquine, hydroxychloroquine or interferons. Controlled clinical trials of these candidate drugs are needed in search of effective COVID-19 treatment in current crisis.</AbstractText><CopyrightInformation>© 2020 The Author(s).</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Guobing</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Center of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing 100191, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ruan</LastName><ForeName>Shasha</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Clinical Oncology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>The First Clinical College of Wuhan University, Wuhan, Hubei 430060, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhao</LastName><ForeName>Xiaolu</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>Qi</ForeName><Initials>Q</Initials><AffiliationInfo><Affiliation>Stem Cell Program, Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dou</LastName><ForeName>Yali</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mao</LastName><ForeName>Fengbiao</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Center of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing 100191, China.</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>06</Day></ArticleDate></Article><MedlineJournalInfo><Country>Netherlands</Country><MedlineTA>Comput Struct Biotechnol J</MedlineTA><NlmUniqueID>101585369</NlmUniqueID><ISSNLinking>2001-0370</ISSNLinking></MedlineJournalInfo><CoiStatement>The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year><Month>09</Month><Day>07</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2020</Year><Month>11</Month><Day>24</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2020</Year><Month>11</Month><Day>28</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>12</Month><Day>15</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>12</Month><Day>15</Day><Hour>6</Hour><Minute>1</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>12</Month><Day>14</Day><Hour>10</Hour><Minute>57</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">33312453</ArticleId><ArticleId IdType="doi">10.1016/j.csbj.2020.11.056</ArticleId><ArticleId IdType="pii">S2001-0370(20)30523-7</ArticleId><ArticleId IdType="pmc">PMC7719282</ArticleId></ArticleIdList><pmc-dir>pmcsd</pmc-dir>
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HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Corpus/RBID.i -Sk "pubmed:33312453" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Corpus/biblio.hfd \
| NlmPubMed2Wicri -a CovidChloroV1
| This area was generated with Dilib version V0.6.38. |  |