COVID-19 Drugs Chloroquine and Hydroxychloroquine, but Not Azithromycin and Remdesivir, Block hERG Potassium Channels.
Identifieur interne : 000271 ( Main/Corpus ); précédent : 000270; suivant : 000272COVID-19 Drugs Chloroquine and Hydroxychloroquine, but Not Azithromycin and Remdesivir, Block hERG Potassium Channels.
Auteurs : Mark Szendrey ; Jun Guo ; Wentao Li ; Tonghua Yang ; Shetuan ZhangSource :
- The Journal of pharmacology and experimental therapeutics [ 1521-0103 ] ; 2021.
English descriptors
- KwdEn :
- Adenosine Monophosphate (analogs & derivatives), Adenosine Monophosphate (pharmacology), Adenosine Monophosphate (therapeutic use), Alanine (analogs & derivatives), Alanine (pharmacology), Alanine (therapeutic use), Anti-Bacterial Agents (pharmacology), Anti-Bacterial Agents (therapeutic use), Antimalarials (pharmacology), Antimalarials (therapeutic use), Antiviral Agents (pharmacology), Antiviral Agents (therapeutic use), Azithromycin (pharmacology), Azithromycin (therapeutic use), COVID-19 (drug therapy), COVID-19 (metabolism), Chloroquine (pharmacology), Chloroquine (therapeutic use), Dose-Response Relationship, Drug (MeSH), ERG1 Potassium Channel (antagonists & inhibitors), ERG1 Potassium Channel (metabolism), HEK293 Cells (MeSH), Humans (MeSH), Hydroxychloroquine (pharmacology), Hydroxychloroquine (therapeutic use), Potassium Channel Blockers (pharmacology), Potassium Channel Blockers (therapeutic use).
- MESH :
- chemical , analogs & derivatives : Adenosine Monophosphate, Alanine.
- chemical , antagonists & inhibitors : ERG1 Potassium Channel.
- chemical , metabolism : ERG1 Potassium Channel.
- chemical , pharmacology : Adenosine Monophosphate, Alanine, Anti-Bacterial Agents, Antimalarials, Antiviral Agents, Azithromycin, Chloroquine, Hydroxychloroquine, Potassium Channel Blockers.
- chemical , therapeutic use : Adenosine Monophosphate, Alanine, Anti-Bacterial Agents, Antimalarials, Antiviral Agents, Azithromycin, Chloroquine, Hydroxychloroquine, Potassium Channel Blockers.
- drug therapy : COVID-19.
- metabolism : COVID-19.
- Dose-Response Relationship, Drug, HEK293 Cells, Humans.
Abstract
Drug-induced long QT syndrome (LQTS) is an established cardiac side effect of a wide range of medications and represents a significant concern for drug safety. The rapidly and slowly activating delayed rectifier K+ currents, mediated by channels encoded by the human ether-a-go-go-related gene (hERG) and KCNQ1 + KCNE1, respectively, are two main currents responsible for ventricular repolarization. The common cause for drugs to induce LQTS is through impairing the hERG channel. For the recent emergence of COVID-19, caused by severe acute respiratory syndrome coronavirus 2, several drugs have been investigated as potential therapies; however, there are concerns about their QT prolongation risk. Here, we studied the effects of chloroquine, hydroxychloroquine, azithromycin, and remdesivir on hERG channels. Our results showed that although chloroquine acutely blocked hERG current (IhERG), with an IC50 of 3.0 µM, hydroxychloroquine acutely blocked IhERG 8-fold less potently, with an IC50 of 23.4 µM. Azithromycin and remdesivir did not acutely affect IhERG When these drugs were added at 10 µM to the cell culture medium for 24 hours, remdesivir increased IhERG by 2-fold, which was associated with an increased mature hERG channel expression. In addition, these four drugs did not acutely or chronically affect KCNQ1 + KCNE1 channels. Our data provide insight into COVID-19 drug-associated LQTS and cardiac safety concerns. SIGNIFICANCE STATEMENT: This work demonstrates that, among off-label potential COVID-19 treatment drugs chloroquine, hydroxychloroquine, azithromycin, and remdesivir, the former two drugs block hERG potassium channels, whereas the latter two drugs do not. All four drugs do not affect KCNQ1 + KCNE1. As hERG and KCNQ1 + KCNE1 are two main K+ channels responsible for ventricular repolarization, and most drugs that induce long QT syndrome (LQTS) do so by impairing hERG channels, these data provide insight into COVID-19 drug-associated LQTS and cardiac safety concerns.
DOI: 10.1124/jpet.120.000484
PubMed: 33674391
Links to Exploration step
pubmed:33674391Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">COVID-19 Drugs Chloroquine and Hydroxychloroquine, but Not Azithromycin and Remdesivir, Block hERG Potassium Channels.</title><author><name sortKey="Szendrey, Mark" sort="Szendrey, Mark" uniqKey="Szendrey M" first="Mark" last="Szendrey">Mark Szendrey</name><affiliation><nlm:affiliation>Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Guo, Jun" sort="Guo, Jun" uniqKey="Guo J" first="Jun" last="Guo">Jun Guo</name><affiliation><nlm:affiliation>Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Li, Wentao" sort="Li, Wentao" uniqKey="Li W" first="Wentao" last="Li">Wentao Li</name><affiliation><nlm:affiliation>Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Yang, Tonghua" sort="Yang, Tonghua" uniqKey="Yang T" first="Tonghua" last="Yang">Tonghua Yang</name><affiliation><nlm:affiliation>Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Zhang, Shetuan" sort="Zhang, Shetuan" uniqKey="Zhang S" first="Shetuan" last="Zhang">Shetuan Zhang</name><affiliation><nlm:affiliation>Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada shetuan.zhang@queensu.ca.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2021">2021</date><idno type="RBID">pubmed:33674391</idno><idno type="pmid">33674391</idno><idno type="doi">10.1124/jpet.120.000484</idno><idno type="wicri:Area/Main/Corpus">000271</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000271</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">COVID-19 Drugs Chloroquine and Hydroxychloroquine, but Not Azithromycin and Remdesivir, Block hERG Potassium Channels.</title><author><name sortKey="Szendrey, Mark" sort="Szendrey, Mark" uniqKey="Szendrey M" first="Mark" last="Szendrey">Mark Szendrey</name><affiliation><nlm:affiliation>Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Guo, Jun" sort="Guo, Jun" uniqKey="Guo J" first="Jun" last="Guo">Jun Guo</name><affiliation><nlm:affiliation>Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Li, Wentao" sort="Li, Wentao" uniqKey="Li W" first="Wentao" last="Li">Wentao Li</name><affiliation><nlm:affiliation>Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Yang, Tonghua" sort="Yang, Tonghua" uniqKey="Yang T" first="Tonghua" last="Yang">Tonghua Yang</name><affiliation><nlm:affiliation>Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Zhang, Shetuan" sort="Zhang, Shetuan" uniqKey="Zhang S" first="Shetuan" last="Zhang">Shetuan Zhang</name><affiliation><nlm:affiliation>Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada shetuan.zhang@queensu.ca.</nlm:affiliation></affiliation></author></analytic><series><title level="j">The Journal of pharmacology and experimental therapeutics</title><idno type="eISSN">1521-0103</idno><imprint><date when="2021" type="published">2021</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adenosine Monophosphate (analogs & derivatives)</term><term>Adenosine Monophosphate (pharmacology)</term><term>Adenosine Monophosphate (therapeutic use)</term><term>Alanine (analogs & derivatives)</term><term>Alanine (pharmacology)</term><term>Alanine (therapeutic use)</term><term>Anti-Bacterial Agents (pharmacology)</term><term>Anti-Bacterial Agents (therapeutic use)</term><term>Antimalarials (pharmacology)</term><term>Antimalarials (therapeutic use)</term><term>Antiviral Agents (pharmacology)</term><term>Antiviral Agents (therapeutic use)</term><term>Azithromycin (pharmacology)</term><term>Azithromycin (therapeutic use)</term><term>COVID-19 (drug therapy)</term><term>COVID-19 (metabolism)</term><term>Chloroquine (pharmacology)</term><term>Chloroquine (therapeutic use)</term><term>Dose-Response Relationship, Drug (MeSH)</term><term>ERG1 Potassium Channel (antagonists & inhibitors)</term><term>ERG1 Potassium Channel (metabolism)</term><term>HEK293 Cells (MeSH)</term><term>Humans (MeSH)</term><term>Hydroxychloroquine (pharmacology)</term><term>Hydroxychloroquine (therapeutic use)</term><term>Potassium Channel Blockers (pharmacology)</term><term>Potassium Channel Blockers (therapeutic use)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Adenosine Monophosphate</term><term>Alanine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>ERG1 Potassium Channel</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>ERG1 Potassium Channel</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Adenosine Monophosphate</term><term>Alanine</term><term>Anti-Bacterial Agents</term><term>Antimalarials</term><term>Antiviral Agents</term><term>Azithromycin</term><term>Chloroquine</term><term>Hydroxychloroquine</term><term>Potassium Channel Blockers</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Adenosine Monophosphate</term><term>Alanine</term><term>Anti-Bacterial Agents</term><term>Antimalarials</term><term>Antiviral Agents</term><term>Azithromycin</term><term>Chloroquine</term><term>Hydroxychloroquine</term><term>Potassium Channel Blockers</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>COVID-19</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>COVID-19</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Dose-Response Relationship, Drug</term><term>HEK293 Cells</term><term>Humans</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Drug-induced long QT syndrome (LQTS) is an established cardiac side effect of a wide range of medications and represents a significant concern for drug safety. The rapidly and slowly activating delayed rectifier K<sup>+</sup> currents, mediated by channels encoded by the human ether-a-go-go-related gene (<i>hERG</i>) and KCNQ1 + KCNE1, respectively, are two main currents responsible for ventricular repolarization. The common cause for drugs to induce LQTS is through impairing the hERG channel. For the recent emergence of COVID-19, caused by severe acute respiratory syndrome coronavirus 2, several drugs have been investigated as potential therapies; however, there are concerns about their QT prolongation risk. Here, we studied the effects of chloroquine, hydroxychloroquine, azithromycin, and remdesivir on hERG channels. Our results showed that although chloroquine acutely blocked hERG current (I<sub>hERG</sub>), with an IC<sub>50</sub> of 3.0 µM, hydroxychloroquine acutely blocked I<sub>hERG</sub> 8-fold less potently, with an IC<sub>50</sub> of 23.4 µM. Azithromycin and remdesivir did not acutely affect I<sub>hERG</sub> When these drugs were added at 10 µM to the cell culture medium for 24 hours, remdesivir increased I<sub>hERG</sub> by 2-fold, which was associated with an increased mature hERG channel expression. In addition, these four drugs did not acutely or chronically affect KCNQ1 + KCNE1 channels. Our data provide insight into COVID-19 drug-associated LQTS and cardiac safety concerns. SIGNIFICANCE STATEMENT: This work demonstrates that, among off-label potential COVID-19 treatment drugs chloroquine, hydroxychloroquine, azithromycin, and remdesivir, the former two drugs block hERG potassium channels, whereas the latter two drugs do not. All four drugs do not affect KCNQ1 + KCNE1. As hERG and KCNQ1 + KCNE1 are two main K<sup>+</sup> channels responsible for ventricular repolarization, and most drugs that induce long QT syndrome (LQTS) do so by impairing hERG channels, these data provide insight into COVID-19 drug-associated LQTS and cardiac safety concerns.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">33674391</PMID><DateCompleted><Year>2021</Year><Month>05</Month><Day>03</Day></DateCompleted><DateRevised><Year>2021</Year><Month>05</Month><Day>03</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1521-0103</ISSN><JournalIssue CitedMedium="Internet"><Volume>377</Volume><Issue>2</Issue><PubDate><Year>2021</Year><Month>05</Month></PubDate></JournalIssue><Title>The Journal of pharmacology and experimental therapeutics</Title><ISOAbbreviation>J Pharmacol Exp Ther</ISOAbbreviation></Journal><ArticleTitle>COVID-19 Drugs Chloroquine and Hydroxychloroquine, but Not Azithromycin and Remdesivir, Block hERG Potassium Channels.</ArticleTitle><Pagination><MedlinePgn>265-272</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1124/jpet.120.000484</ELocationID><Abstract><AbstractText>Drug-induced long QT syndrome (LQTS) is an established cardiac side effect of a wide range of medications and represents a significant concern for drug safety. The rapidly and slowly activating delayed rectifier K<sup>+</sup> currents, mediated by channels encoded by the human ether-a-go-go-related gene (<i>hERG</i>) and KCNQ1 + KCNE1, respectively, are two main currents responsible for ventricular repolarization. The common cause for drugs to induce LQTS is through impairing the hERG channel. For the recent emergence of COVID-19, caused by severe acute respiratory syndrome coronavirus 2, several drugs have been investigated as potential therapies; however, there are concerns about their QT prolongation risk. Here, we studied the effects of chloroquine, hydroxychloroquine, azithromycin, and remdesivir on hERG channels. Our results showed that although chloroquine acutely blocked hERG current (I<sub>hERG</sub>), with an IC<sub>50</sub> of 3.0 µM, hydroxychloroquine acutely blocked I<sub>hERG</sub> 8-fold less potently, with an IC<sub>50</sub> of 23.4 µM. Azithromycin and remdesivir did not acutely affect I<sub>hERG</sub> When these drugs were added at 10 µM to the cell culture medium for 24 hours, remdesivir increased I<sub>hERG</sub> by 2-fold, which was associated with an increased mature hERG channel expression. In addition, these four drugs did not acutely or chronically affect KCNQ1 + KCNE1 channels. Our data provide insight into COVID-19 drug-associated LQTS and cardiac safety concerns. SIGNIFICANCE STATEMENT: This work demonstrates that, among off-label potential COVID-19 treatment drugs chloroquine, hydroxychloroquine, azithromycin, and remdesivir, the former two drugs block hERG potassium channels, whereas the latter two drugs do not. All four drugs do not affect KCNQ1 + KCNE1. As hERG and KCNQ1 + KCNE1 are two main K<sup>+</sup> channels responsible for ventricular repolarization, and most drugs that induce long QT syndrome (LQTS) do so by impairing hERG channels, these data provide insight into COVID-19 drug-associated LQTS and cardiac safety concerns.</AbstractText><CopyrightInformation>Copyright © 2021 by The American Society for Pharmacology and Experimental Therapeutics.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Szendrey</LastName><ForeName>Mark</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Guo</LastName><ForeName>Jun</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Wentao</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yang</LastName><ForeName>Tonghua</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Shetuan</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada shetuan.zhang@queensu.ca.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2021</Year><Month>03</Month><Day>05</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>J Pharmacol Exp Ther</MedlineTA><NlmUniqueID>0376362</NlmUniqueID><ISSNLinking>0022-3565</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000900">Anti-Bacterial Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000962">Antimalarials</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000998">Antiviral Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000072237">ERG1 Potassium Channel</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C000606913">KCNH2 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D026902">Potassium Channel Blockers</NameOfSubstance></Chemical><Chemical><RegistryNumber>3QKI37EEHE</RegistryNumber><NameOfSubstance UI="C000606551">remdesivir</NameOfSubstance></Chemical><Chemical><RegistryNumber>415SHH325A</RegistryNumber><NameOfSubstance UI="D000249">Adenosine Monophosphate</NameOfSubstance></Chemical><Chemical><RegistryNumber>4QWG6N8QKH</RegistryNumber><NameOfSubstance UI="D006886">Hydroxychloroquine</NameOfSubstance></Chemical><Chemical><RegistryNumber>83905-01-5</RegistryNumber><NameOfSubstance UI="D017963">Azithromycin</NameOfSubstance></Chemical><Chemical><RegistryNumber>886U3H6UFF</RegistryNumber><NameOfSubstance UI="D002738">Chloroquine</NameOfSubstance></Chemical><Chemical><RegistryNumber>OF5P57N2ZX</RegistryNumber><NameOfSubstance UI="D000409">Alanine</NameOfSubstance></Chemical></ChemicalList><SupplMeshList><SupplMeshName Type="Protocol" UI="C000705127">COVID-19 drug treatment</SupplMeshName></SupplMeshList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000249" MajorTopicYN="N">Adenosine Monophosphate</DescriptorName><QualifierName UI="Q000031" MajorTopicYN="Y">analogs & derivatives</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000409" MajorTopicYN="N">Alanine</DescriptorName><QualifierName UI="Q000031" MajorTopicYN="Y">analogs & derivatives</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000900" MajorTopicYN="N">Anti-Bacterial Agents</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000962" MajorTopicYN="N">Antimalarials</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000998" MajorTopicYN="N">Antiviral Agents</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D017963" MajorTopicYN="N">Azithromycin</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000086382" MajorTopicYN="N">COVID-19</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002738" MajorTopicYN="N">Chloroquine</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004305" MajorTopicYN="N">Dose-Response Relationship, Drug</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000072237" MajorTopicYN="N">ERG1 Potassium Channel</DescriptorName><QualifierName UI="Q000037" MajorTopicYN="Y">antagonists & inhibitors</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D057809" MajorTopicYN="N">HEK293 Cells</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006886" MajorTopicYN="N">Hydroxychloroquine</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D026902" MajorTopicYN="N">Potassium Channel Blockers</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading></MeshHeadingList><CoiStatement>The authors declare that they have no conflicts of interest with the contents of this article.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year><Month>12</Month><Day>23</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2021</Year><Month>03</Month><Day>02</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2021</Year><Month>3</Month><Day>7</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate 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