In vitro activity of lopinavir/ritonavir and hydroxychloroquine against severe acute respiratory syndrome coronavirus 2 at concentrations achievable by usual doses.
Identifieur interne : 001572 ( Main/Corpus ); précédent : 001571; suivant : 001573In vitro activity of lopinavir/ritonavir and hydroxychloroquine against severe acute respiratory syndrome coronavirus 2 at concentrations achievable by usual doses.
Auteurs : Chang Kyung Kang ; Moon-Woo Seong ; Su-Jin Choi ; Taek Soo Kim ; Pyoeng Gyun Choe ; Sang Hoon Song ; Nam-Joong Kim ; Wan Beom Park ; Myoung-Don OhSource :
- The Korean journal of internal medicine [ 2005-6648 ] ; 2020.
English descriptors
- KwdEn :
- MESH :
- chemical : Anti-Infective Agents, Drug Combinations, Hydroxychloroquine, Lopinavir, Ritonavir.
- drug effects : Betacoronavirus.
- Animals, Chlorocebus aethiops, Microbial Sensitivity Tests, SARS-CoV-2, Vero Cells.
Abstract
BACKGROUND/AIMS
As the coronavirus disease-2019 global pandemic progresses, screening of antiviral agents effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is urgently needed. In addition, considering the viral load kinetics of SARS-CoV-2, which peaks early in the illness, and the massive burden of the disease, which may increase in the near future, identifying well-tolerated oral antivirals becomes increasingly important. We examined the in vitro activity of lopinavir/ritonavir and hydroxychloroquine on SARS-CoV-2, at concentrations which can be used to treat coronavirus-19 patients with little concern of toxicity.
METHODS
Lopinavir/ritonavir (7/1.75 μg/mL), hydroxychloroquine base (1 or 2 μg/mL), or a combination thereof were administered 1 hour after the inoculation of SARS-CoV-2 to Vero cells at a multiplicity of infection of 0.05. We examined cytopathic effects of virus 48 hours after administration of the respective treatments and measured viral loads at three time points (0, 24, and 48 hours post-treatment) by quantitative real-time reverse-transcription polymerase chain reaction, and compared the results obtained from the different antiviral regimens tested.
RESULTS
The severity of cytopathic effects was lower in lopinavir/ritonavir-treated cells, and viral load was significantly reduced in this group compared with the control group (p < 0.001). However, hydroxychloroquine did not show significant inhibitory effects on anti-SARS-CoV-2-mediated cytotoxicity or on viral load at either concentration.
CONCLUSION
Lopinavir/ritonavir showed significant inhibitory effects on SARS-CoV-2 in vitro at its usual plasma concentration. However, the in vitro antiviral activity of hydroxychloroquine at concentrations commonly used in humans was minimal, whether used alone or in combination with lopinavir/ritonavir.
DOI: 10.3904/kjim.2020.157
PubMed: 32460458
PubMed Central: PMC7373950
Links to Exploration step
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of Infection & Immunity, Seoul National University Hospital Biomedical Research Institute, Seoul, Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Kim, Taek Soo" sort="Kim, Taek Soo" uniqKey="Kim T" first="Taek Soo" last="Kim">Taek Soo Kim</name><affiliation><nlm:affiliation>Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Choe, Pyoeng Gyun" sort="Choe, Pyoeng Gyun" uniqKey="Choe P" first="Pyoeng Gyun" last="Choe">Pyoeng Gyun Choe</name><affiliation><nlm:affiliation>Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Song, Sang Hoon" sort="Song, Sang Hoon" uniqKey="Song S" first="Sang Hoon" last="Song">Sang Hoon Song</name><affiliation><nlm:affiliation>Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Kim, Nam Joong" sort="Kim, Nam Joong" uniqKey="Kim N" first="Nam-Joong" last="Kim">Nam-Joong Kim</name><affiliation><nlm:affiliation>Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Park, Wan Beom" sort="Park, Wan Beom" uniqKey="Park W" first="Wan Beom" last="Park">Wan Beom Park</name><affiliation><nlm:affiliation>Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Oh, Myoung Don" sort="Oh, Myoung Don" uniqKey="Oh M" first="Myoung-Don" last="Oh">Myoung-Don Oh</name><affiliation><nlm:affiliation>Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:32460458</idno><idno type="pmid">32460458</idno><idno type="doi">10.3904/kjim.2020.157</idno><idno type="pmc">PMC7373950</idno><idno type="wicri:Area/Main/Corpus">001572</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">001572</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">In vitro activity of lopinavir/ritonavir and hydroxychloroquine against severe acute respiratory syndrome coronavirus 2 at concentrations achievable by usual doses.</title><author><name sortKey="Kang, Chang Kyung" sort="Kang, Chang Kyung" uniqKey="Kang C" first="Chang Kyung" last="Kang">Chang Kyung Kang</name><affiliation><nlm:affiliation>Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Seong, Moon Woo" sort="Seong, Moon Woo" uniqKey="Seong M" first="Moon-Woo" last="Seong">Moon-Woo Seong</name><affiliation><nlm:affiliation>Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Choi, Su Jin" sort="Choi, Su Jin" uniqKey="Choi S" first="Su-Jin" last="Choi">Su-Jin Choi</name><affiliation><nlm:affiliation>Laboratory of Infection & Immunity, Seoul National University Hospital Biomedical Research Institute, Seoul, Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Kim, Taek Soo" sort="Kim, Taek Soo" uniqKey="Kim T" first="Taek Soo" last="Kim">Taek Soo Kim</name><affiliation><nlm:affiliation>Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Choe, Pyoeng Gyun" sort="Choe, Pyoeng Gyun" uniqKey="Choe P" first="Pyoeng Gyun" last="Choe">Pyoeng Gyun Choe</name><affiliation><nlm:affiliation>Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Song, Sang Hoon" sort="Song, Sang Hoon" uniqKey="Song S" first="Sang Hoon" last="Song">Sang Hoon Song</name><affiliation><nlm:affiliation>Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Kim, Nam Joong" sort="Kim, Nam Joong" uniqKey="Kim N" first="Nam-Joong" last="Kim">Nam-Joong Kim</name><affiliation><nlm:affiliation>Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Park, Wan Beom" sort="Park, Wan Beom" uniqKey="Park W" first="Wan Beom" last="Park">Wan Beom Park</name><affiliation><nlm:affiliation>Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Oh, Myoung Don" sort="Oh, Myoung Don" uniqKey="Oh M" first="Myoung-Don" last="Oh">Myoung-Don Oh</name><affiliation><nlm:affiliation>Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.</nlm:affiliation></affiliation></author></analytic><series><title level="j">The Korean journal of internal medicine</title><idno type="eISSN">2005-6648</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals (MeSH)</term><term>Anti-Infective Agents (MeSH)</term><term>Betacoronavirus (drug effects)</term><term>Chlorocebus aethiops (MeSH)</term><term>Drug Combinations (MeSH)</term><term>Hydroxychloroquine (MeSH)</term><term>Lopinavir (MeSH)</term><term>Microbial Sensitivity Tests (MeSH)</term><term>Ritonavir (MeSH)</term><term>SARS-CoV-2 (MeSH)</term><term>Vero Cells (MeSH)</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>Anti-Infective Agents</term><term>Drug Combinations</term><term>Hydroxychloroquine</term><term>Lopinavir</term><term>Ritonavir</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Betacoronavirus</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Chlorocebus aethiops</term><term>Microbial Sensitivity Tests</term><term>SARS-CoV-2</term><term>Vero Cells</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><b>BACKGROUND/AIMS</b></p><p>As the coronavirus disease-2019 global pandemic progresses, screening of antiviral agents effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is urgently needed. In addition, considering the viral load kinetics of SARS-CoV-2, which peaks early in the illness, and the massive burden of the disease, which may increase in the near future, identifying well-tolerated oral antivirals becomes increasingly important. We examined the in vitro activity of lopinavir/ritonavir and hydroxychloroquine on SARS-CoV-2, at concentrations which can be used to treat coronavirus-19 patients with little concern of toxicity.</p></div><div type="abstract" xml:lang="en"><p><b>METHODS</b></p><p>Lopinavir/ritonavir (7/1.75 μg/mL), hydroxychloroquine base (1 or 2 μg/mL), or a combination thereof were administered 1 hour after the inoculation of SARS-CoV-2 to Vero cells at a multiplicity of infection of 0.05. We examined cytopathic effects of virus 48 hours after administration of the respective treatments and measured viral loads at three time points (0, 24, and 48 hours post-treatment) by quantitative real-time reverse-transcription polymerase chain reaction, and compared the results obtained from the different antiviral regimens tested.</p></div><div type="abstract" xml:lang="en"><p><b>RESULTS</b></p><p>The severity of cytopathic effects was lower in lopinavir/ritonavir-treated cells, and viral load was significantly reduced in this group compared with the control group (p < 0.001). However, hydroxychloroquine did not show significant inhibitory effects on anti-SARS-CoV-2-mediated cytotoxicity or on viral load at either concentration.</p></div><div type="abstract" xml:lang="en"><p><b>CONCLUSION</b></p><p>Lopinavir/ritonavir showed significant inhibitory effects on SARS-CoV-2 in vitro at its usual plasma concentration. However, the in vitro antiviral activity of hydroxychloroquine at concentrations commonly used in humans was minimal, whether used alone or in combination with lopinavir/ritonavir.</p></div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">32460458</PMID><DateCompleted><Year>2020</Year><Month>07</Month><Day>28</Day></DateCompleted><DateRevised><Year>2020</Year><Month>12</Month><Day>18</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">2005-6648</ISSN><JournalIssue CitedMedium="Internet"><Volume>35</Volume><Issue>4</Issue><PubDate><Year>2020</Year><Month>07</Month></PubDate></JournalIssue><Title>The Korean journal of internal medicine</Title><ISOAbbreviation>Korean J Intern Med</ISOAbbreviation></Journal><ArticleTitle>In vitro activity of lopinavir/ritonavir and hydroxychloroquine against severe acute respiratory syndrome coronavirus 2 at concentrations achievable by usual doses.</ArticleTitle><Pagination><MedlinePgn>782-787</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.3904/kjim.2020.157</ELocationID><Abstract><AbstractText Label="BACKGROUND/AIMS">As the coronavirus disease-2019 global pandemic progresses, screening of antiviral agents effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is urgently needed. In addition, considering the viral load kinetics of SARS-CoV-2, which peaks early in the illness, and the massive burden of the disease, which may increase in the near future, identifying well-tolerated oral antivirals becomes increasingly important. We examined the in vitro activity of lopinavir/ritonavir and hydroxychloroquine on SARS-CoV-2, at concentrations which can be used to treat coronavirus-19 patients with little concern of toxicity.</AbstractText><AbstractText Label="METHODS">Lopinavir/ritonavir (7/1.75 μg/mL), hydroxychloroquine base (1 or 2 μg/mL), or a combination thereof were administered 1 hour after the inoculation of SARS-CoV-2 to Vero cells at a multiplicity of infection of 0.05. We examined cytopathic effects of virus 48 hours after administration of the respective treatments and measured viral loads at three time points (0, 24, and 48 hours post-treatment) by quantitative real-time reverse-transcription polymerase chain reaction, and compared the results obtained from the different antiviral regimens tested.</AbstractText><AbstractText Label="RESULTS">The severity of cytopathic effects was lower in lopinavir/ritonavir-treated cells, and viral load was significantly reduced in this group compared with the control group (p < 0.001). However, hydroxychloroquine did not show significant inhibitory effects on anti-SARS-CoV-2-mediated cytotoxicity or on viral load at either concentration.</AbstractText><AbstractText Label="CONCLUSION">Lopinavir/ritonavir showed significant inhibitory effects on SARS-CoV-2 in vitro at its usual plasma concentration. However, the in vitro antiviral activity of hydroxychloroquine at concentrations commonly used in humans was minimal, whether used alone or in combination with lopinavir/ritonavir.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Kang</LastName><ForeName>Chang Kyung</ForeName><Initials>CK</Initials><AffiliationInfo><Affiliation>Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Seong</LastName><ForeName>Moon-Woo</ForeName><Initials>MW</Initials><AffiliationInfo><Affiliation>Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Choi</LastName><ForeName>Su-Jin</ForeName><Initials>SJ</Initials><AffiliationInfo><Affiliation>Laboratory of Infection & Immunity, Seoul National University Hospital Biomedical Research Institute, Seoul, Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kim</LastName><ForeName>Taek Soo</ForeName><Initials>TS</Initials><AffiliationInfo><Affiliation>Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Choe</LastName><ForeName>Pyoeng Gyun</ForeName><Initials>PG</Initials><AffiliationInfo><Affiliation>Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Song</LastName><ForeName>Sang Hoon</ForeName><Initials>SH</Initials><AffiliationInfo><Affiliation>Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kim</LastName><ForeName>Nam-Joong</ForeName><Initials>NJ</Initials><AffiliationInfo><Affiliation>Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Park</LastName><ForeName>Wan Beom</ForeName><Initials>WB</Initials><AffiliationInfo><Affiliation>Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Oh</LastName><ForeName>Myoung-Don</ForeName><Initials>MD</Initials><AffiliationInfo><Affiliation>Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>05</Month><Day>29</Day></ArticleDate></Article><MedlineJournalInfo><Country>Korea (South)</Country><MedlineTA>Korean J Intern 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MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000890" MajorTopicYN="Y">Anti-Infective Agents</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000073640" MajorTopicYN="N">Betacoronavirus</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002522" MajorTopicYN="N">Chlorocebus aethiops</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004338" MajorTopicYN="N">Drug Combinations</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006886" MajorTopicYN="Y">Hydroxychloroquine</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D061466" MajorTopicYN="Y">Lopinavir</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008826" MajorTopicYN="N">Microbial Sensitivity Tests</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D019438" 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PubStatus="medline"><Year>2020</Year><Month>7</Month><Day>29</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>5</Month><Day>29</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">32460458</ArticleId><ArticleId IdType="pii">kjim.2020.157</ArticleId><ArticleId IdType="doi">10.3904/kjim.2020.157</ArticleId><ArticleId IdType="pmc">PMC7373950</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>CMAJ. 2020 Apr 27;192(17):E450-E453</Citation><ArticleIdList><ArticleId IdType="pubmed">32269021</ArticleId></ArticleIdList></Reference><Reference><Citation>Zhejiang Da Xue Xue Bao Yi Xue Ban. 2020 May 25;49(2):215-219</Citation><ArticleIdList><ArticleId IdType="pubmed">32391667</ArticleId></ArticleIdList></Reference><Reference><Citation>J Korean Med Sci. 2020 Feb 24;35(7):e84</Citation><ArticleIdList><ArticleId IdType="pubmed">32080990</ArticleId></ArticleIdList></Reference><Reference><Citation>J Virol Methods. 2015 Oct;223:13-8</Citation><ArticleIdList><ArticleId IdType="pubmed">26190637</ArticleId></ArticleIdList></Reference><Reference><Citation>N Engl J Med. 2020 Mar 19;382(12):1177-1179</Citation><ArticleIdList><ArticleId IdType="pubmed">32074444</ArticleId></ArticleIdList></Reference><Reference><Citation>Clin Transl Sci. 2020 Jul;13(4):642-645</Citation><ArticleIdList><ArticleId IdType="pubmed">32268005</ArticleId></ArticleIdList></Reference><Reference><Citation>Arthritis Rheumatol. 2015 May;67(8):2176-84</Citation><ArticleIdList><ArticleId IdType="pubmed">25989906</ArticleId></ArticleIdList></Reference><Reference><Citation>Int J Antimicrob Agents. 2020 Jul;56(1):105949</Citation><ArticleIdList><ArticleId IdType="pubmed">32205204</ArticleId></ArticleIdList></Reference><Reference><Citation>Drug Saf. 2018 Oct;41(10):919-931</Citation><ArticleIdList><ArticleId IdType="pubmed">29858838</ArticleId></ArticleIdList></Reference><Reference><Citation>Antiviral Res. 2020 Jun;178:104786</Citation><ArticleIdList><ArticleId IdType="pubmed">32251767</ArticleId></ArticleIdList></Reference><Reference><Citation>N Engl J Med. 2020 May 7;382(19):1787-1799</Citation><ArticleIdList><ArticleId IdType="pubmed">32187464</ArticleId></ArticleIdList></Reference><Reference><Citation>Clin Infect Dis. 2020 Jul 28;71(15):732-739</Citation><ArticleIdList><ArticleId IdType="pubmed">32150618</ArticleId></ArticleIdList></Reference><Reference><Citation>J Infect Dis. 2015 Dec 15;212(12):1904-13</Citation><ArticleIdList><ArticleId IdType="pubmed">26198719</ArticleId></ArticleIdList></Reference><Reference><Citation>Travel Med Infect Dis. 2020 Mar - Apr;34:101663</Citation><ArticleIdList><ArticleId IdType="pubmed">32289548</ArticleId></ArticleIdList></Reference><Reference><Citation>Lancet Infect Dis. 2020 Apr;20(4):411-412</Citation><ArticleIdList><ArticleId IdType="pubmed">32105638</ArticleId></ArticleIdList></Reference><Reference><Citation>Thorax. 2004 Mar;59(3):252-6</Citation><ArticleIdList><ArticleId IdType="pubmed">14985565</ArticleId></ArticleIdList></Reference><Reference><Citation>Cell Discov. 2020 Mar 18;6:16</Citation><ArticleIdList><ArticleId IdType="pubmed">32194981</ArticleId></ArticleIdList></Reference><Reference><Citation>Virol J. 2005 Aug 22;2:69</Citation><ArticleIdList><ArticleId IdType="pubmed">16115318</ArticleId></ArticleIdList></Reference><Reference><Citation>AIDS. 2004 Mar 26;18(5):775-9</Citation><ArticleIdList><ArticleId IdType="pubmed">15075512</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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