System biological investigations of hydroxychloroquine and azithromycin targets and their implications in QT interval prolongation.
Identifieur interne : 000953 ( Main/Corpus ); précédent : 000952; suivant : 000954System biological investigations of hydroxychloroquine and azithromycin targets and their implications in QT interval prolongation.
Auteurs : Abdul Arif Khan ; Zakir KhanSource :
- Chemico-biological interactions [ 1872-7786 ] ; 2020.
English descriptors
- KwdEn :
- Azithromycin (adverse effects), Azithromycin (therapeutic use), COVID-19 (complications), COVID-19 (drug therapy), COVID-19 (epidemiology), Drug Combinations (MeSH), HSP90 Heat-Shock Proteins (genetics), HSP90 Heat-Shock Proteins (metabolism), Humans (MeSH), Hydroxychloroquine (adverse effects), Hydroxychloroquine (therapeutic use), Long QT Syndrome (etiology), Pandemics (MeSH), Protein Interaction Maps (MeSH), Proto-Oncogene Proteins c-akt (genetics), Proto-Oncogene Proteins c-akt (metabolism), SARS-CoV-2 (drug effects), Signal Transduction (drug effects).
- MESH :
- chemical , adverse effects : Azithromycin, Hydroxychloroquine.
- chemical , genetics : HSP90 Heat-Shock Proteins, Proto-Oncogene Proteins c-akt.
- chemical , metabolism : HSP90 Heat-Shock Proteins, Proto-Oncogene Proteins c-akt.
- chemical , therapeutic use : Azithromycin, Hydroxychloroquine.
- complications : COVID-19.
- drug effects : SARS-CoV-2, Signal Transduction.
- drug therapy : COVID-19.
- epidemiology : COVID-19.
- etiology : Long QT Syndrome.
- chemical : Drug Combinations, Humans, Pandemics, Protein Interaction Maps.
Abstract
COVID-2019 pandemic is affecting people worldwide in the absence of an effective treatment strategy. Several suggestive therapeutic options through drug repurposing are recommended, but a complete consensus is not reached. A combination of Hydroxychloroquine (HCQ) and Azithromycin (AZM) has been widely tried and discussed but its administration has also led to potential adversities in patients. Studies are suggesting that most prominent adverse event with HCQ and AZM combination is QT interval prolongation. We studied interaction of HCQ with AZM and subsequent effect of this drug combination on QT interval prolongation. We performed system biological investigation of HCQ and AZM targets and screened important targets and pathways possibly involved in QT interval prolongation. The best core hub protein drug targets involved in QT interval prolongation were identified as HSP90AA1 exclusively associated with HCQ, while AKT1 exclusively associated with AZM on the basis of node degree value. It was found that PI3K/Akt, VEGF, ERBB2 pathways must be given consideration for understanding the role of HCQ and AZM in QT interval prolongation. Conclusion: Computational methods have certain limitations based on source database coverage and prediction algorithms and therefore this data needs experimental correlation to draw final conclusion, but current findings screen targets for QT interval prolongation associated with HCQ and AZM. These proteins and pathways may provide ways to reduce this major risk associated with this combination.
DOI: 10.1016/j.cbi.2020.109299
PubMed: 33098839
PubMed Central: PMC7578186
Links to Exploration step
pubmed:33098839Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">System biological investigations of hydroxychloroquine and azithromycin targets and their implications in QT interval prolongation.</title><author><name sortKey="Khan, Abdul Arif" sort="Khan, Abdul Arif" uniqKey="Khan A" first="Abdul Arif" last="Khan">Abdul Arif Khan</name><affiliation><nlm:affiliation>Indian Council of Medical Research-National AIDS Research Institute, Pune, Maharashtra, 411026, India. Electronic address: abdularifkhan@gmail.com.</nlm:affiliation></affiliation></author><author><name sortKey="Khan, Zakir" sort="Khan, Zakir" uniqKey="Khan Z" first="Zakir" last="Khan">Zakir Khan</name><affiliation><nlm:affiliation>Department of Biomedical Sciences, Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Davis Bldg. Rm. 2014 8700 Beverly Blvd. Los Angeles, CA, 90048, USA.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:33098839</idno><idno type="pmid">33098839</idno><idno type="doi">10.1016/j.cbi.2020.109299</idno><idno type="pmc">PMC7578186</idno><idno type="wicri:Area/Main/Corpus">000953</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000953</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">System biological investigations of hydroxychloroquine and azithromycin targets and their implications in QT interval prolongation.</title><author><name sortKey="Khan, Abdul Arif" sort="Khan, Abdul Arif" uniqKey="Khan A" first="Abdul Arif" last="Khan">Abdul Arif Khan</name><affiliation><nlm:affiliation>Indian Council of Medical Research-National AIDS Research Institute, Pune, Maharashtra, 411026, India. Electronic address: abdularifkhan@gmail.com.</nlm:affiliation></affiliation></author><author><name sortKey="Khan, Zakir" sort="Khan, Zakir" uniqKey="Khan Z" first="Zakir" last="Khan">Zakir Khan</name><affiliation><nlm:affiliation>Department of Biomedical Sciences, Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Davis Bldg. Rm. 2014 8700 Beverly Blvd. Los Angeles, CA, 90048, USA.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Chemico-biological interactions</title><idno type="eISSN">1872-7786</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Azithromycin (adverse effects)</term><term>Azithromycin (therapeutic use)</term><term>COVID-19 (complications)</term><term>COVID-19 (drug therapy)</term><term>COVID-19 (epidemiology)</term><term>Drug Combinations (MeSH)</term><term>HSP90 Heat-Shock Proteins (genetics)</term><term>HSP90 Heat-Shock Proteins (metabolism)</term><term>Humans (MeSH)</term><term>Hydroxychloroquine (adverse effects)</term><term>Hydroxychloroquine (therapeutic use)</term><term>Long QT Syndrome (etiology)</term><term>Pandemics (MeSH)</term><term>Protein Interaction Maps (MeSH)</term><term>Proto-Oncogene Proteins c-akt (genetics)</term><term>Proto-Oncogene Proteins c-akt (metabolism)</term><term>SARS-CoV-2 (drug effects)</term><term>Signal Transduction (drug effects)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Azithromycin</term><term>Hydroxychloroquine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>HSP90 Heat-Shock Proteins</term><term>Proto-Oncogene Proteins c-akt</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>HSP90 Heat-Shock Proteins</term><term>Proto-Oncogene Proteins c-akt</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Azithromycin</term><term>Hydroxychloroquine</term></keywords><keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>COVID-19</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>SARS-CoV-2</term><term>Signal Transduction</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>COVID-19</term></keywords><keywords scheme="MESH" qualifier="epidemiology" xml:lang="en"><term>COVID-19</term></keywords><keywords scheme="MESH" qualifier="etiology" xml:lang="en"><term>Long QT Syndrome</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>Drug Combinations</term><term>Humans</term><term>Pandemics</term><term>Protein Interaction Maps</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">COVID-2019 pandemic is affecting people worldwide in the absence of an effective treatment strategy. Several suggestive therapeutic options through drug repurposing are recommended, but a complete consensus is not reached. A combination of Hydroxychloroquine (HCQ) and Azithromycin (AZM) has been widely tried and discussed but its administration has also led to potential adversities in patients. Studies are suggesting that most prominent adverse event with HCQ and AZM combination is QT interval prolongation. We studied interaction of HCQ with AZM and subsequent effect of this drug combination on QT interval prolongation. We performed system biological investigation of HCQ and AZM targets and screened important targets and pathways possibly involved in QT interval prolongation. The best core hub protein drug targets involved in QT interval prolongation were identified as HSP90AA1 exclusively associated with HCQ, while AKT1 exclusively associated with AZM on the basis of node degree value. It was found that PI3K/Akt, VEGF, ERBB2 pathways must be given consideration for understanding the role of HCQ and AZM in QT interval prolongation. Conclusion: Computational methods have certain limitations based on source database coverage and prediction algorithms and therefore this data needs experimental correlation to draw final conclusion, but current findings screen targets for QT interval prolongation associated with HCQ and AZM. These proteins and pathways may provide ways to reduce this major risk associated with this combination.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">33098839</PMID><DateCompleted><Year>2020</Year><Month>12</Month><Day>08</Day></DateCompleted><DateRevised><Year>2021</Year><Month>01</Month><Day>10</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1872-7786</ISSN><JournalIssue CitedMedium="Internet"><Volume>332</Volume><PubDate><Year>2020</Year><Month>Dec</Month><Day>01</Day></PubDate></JournalIssue><Title>Chemico-biological interactions</Title><ISOAbbreviation>Chem Biol Interact</ISOAbbreviation></Journal><ArticleTitle>System biological investigations of hydroxychloroquine and azithromycin targets and their implications in QT interval prolongation.</ArticleTitle><Pagination><MedlinePgn>109299</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">S0009-2797(20)31579-9</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.cbi.2020.109299</ELocationID><Abstract><AbstractText>COVID-2019 pandemic is affecting people worldwide in the absence of an effective treatment strategy. Several suggestive therapeutic options through drug repurposing are recommended, but a complete consensus is not reached. A combination of Hydroxychloroquine (HCQ) and Azithromycin (AZM) has been widely tried and discussed but its administration has also led to potential adversities in patients. Studies are suggesting that most prominent adverse event with HCQ and AZM combination is QT interval prolongation. We studied interaction of HCQ with AZM and subsequent effect of this drug combination on QT interval prolongation. We performed system biological investigation of HCQ and AZM targets and screened important targets and pathways possibly involved in QT interval prolongation. The best core hub protein drug targets involved in QT interval prolongation were identified as HSP90AA1 exclusively associated with HCQ, while AKT1 exclusively associated with AZM on the basis of node degree value. It was found that PI3K/Akt, VEGF, ERBB2 pathways must be given consideration for understanding the role of HCQ and AZM in QT interval prolongation. Conclusion: Computational methods have certain limitations based on source database coverage and prediction algorithms and therefore this data needs experimental correlation to draw final conclusion, but current findings screen targets for QT interval prolongation associated with HCQ and AZM. These proteins and pathways may provide ways to reduce this major risk associated with this combination.</AbstractText><CopyrightInformation>Copyright © 2020 Elsevier B.V. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Khan</LastName><ForeName>Abdul Arif</ForeName><Initials>AA</Initials><AffiliationInfo><Affiliation>Indian Council of Medical Research-National AIDS Research Institute, Pune, Maharashtra, 411026, India. Electronic address: abdularifkhan@gmail.com.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Khan</LastName><ForeName>Zakir</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>Department of Biomedical Sciences, Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Davis Bldg. Rm. 2014 8700 Beverly Blvd. Los Angeles, CA, 90048, USA.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>10</Month><Day>22</Day></ArticleDate></Article><MedlineJournalInfo><Country>Ireland</Country><MedlineTA>Chem Biol Interact</MedlineTA><NlmUniqueID>0227276</NlmUniqueID><ISSNLinking>0009-2797</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D004338">Drug Combinations</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D018841">HSP90 Heat-Shock Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C112969">HSP90AA1 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>4QWG6N8QKH</RegistryNumber><NameOfSubstance 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