Mefloquine, a Potent Anti-severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2) Drug as an Entry Inhibitor in vitro.
Identifieur interne : 000341 ( Main/Exploration ); précédent : 000340; suivant : 000342Mefloquine, a Potent Anti-severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2) Drug as an Entry Inhibitor in vitro.
Auteurs : Kaho Shionoya [Japon] ; Masako Yamasaki [Japon] ; Shoya Iwanami [Japon] ; Yusuke Ito [Japon] ; Shuetsu Fukushi [Japon] ; Hirofumi Ohashi [Japon] ; Wakana Saso [Japon] ; Tomohiro Tanaka [Japon] ; Shin Aoki [Japon] ; Kouji Kuramochi [Japon] ; Shingo Iwami [Japon] ; Yoshimasa Takahashi [Japon] ; Tadaki Suzuki [Japon] ; Masamichi Muramatsu [Japon] ; Makoto Takeda [Japon] ; Takaji Wakita [Japon] ; Koichi Watashi [Japon]Source :
- Frontiers in microbiology [ 1664-302X ] ; 2021.
Abstract
Coronavirus disease 2019 (COVID-19) has caused serious public health, social, and economic damage worldwide and effective drugs that prevent or cure COVID-19 are urgently needed. Approved drugs including Hydroxychloroquine, Remdesivir or Interferon were reported to inhibit the infection or propagation of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), however, their clinical efficacies have not yet been well demonstrated. To identify drugs with higher antiviral potency, we screened approved anti-parasitic/anti-protozoal drugs and identified an anti-malarial drug, Mefloquine, which showed the highest anti-SARS-CoV-2 activity among the tested compounds. Mefloquine showed higher anti-SARS-CoV-2 activity than Hydroxychloroquine in VeroE6/TMPRSS2 and Calu-3 cells, with IC50 = 1.28 μM, IC90 = 2.31 μM, and IC99 = 4.39 μM in VeroE6/TMPRSS2 cells. Mefloquine inhibited viral entry after viral attachment to the target cell. Combined treatment with Mefloquine and Nelfinavir, a replication inhibitor, showed synergistic antiviral activity. Our mathematical modeling based on the drug concentration in the lung predicted that Mefloquine administration at a standard treatment dosage could decline viral dynamics in patients, reduce cumulative viral load to 7% and shorten the time until virus elimination by 6.1 days. These data cumulatively underscore Mefloquine as an anti-SARS-CoV-2 entry inhibitor.
DOI: 10.3389/fmicb.2021.651403
PubMed: 33995308
PubMed Central: PMC8119653
Affiliations:
- Japon
- Kyūshū, Préfecture de Fukuoka, Région de Kantō, Région du Kansai
- Fukuoka, Kyoto, Tokyo
- Université de Kyoto, Université de Kyūshū, Université de Tokyo
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<author><name sortKey="Iwanami, Shoya" sort="Iwanami, Shoya" uniqKey="Iwanami S" first="Shoya" last="Iwanami">Shoya Iwanami</name>
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<author><name sortKey="Fukushi, Shuetsu" sort="Fukushi, Shuetsu" uniqKey="Fukushi S" first="Shuetsu" last="Fukushi">Shuetsu Fukushi</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Virology I, National Institute of Infectious Diseases, Tokyo, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Department of Virology I, National Institute of Infectious Diseases, Tokyo</wicri:regionArea>
<placeName><settlement type="city">Tokyo</settlement>
<region type="région">Région de Kantō</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Ohashi, Hirofumi" sort="Ohashi, Hirofumi" uniqKey="Ohashi H" first="Hirofumi" last="Ohashi">Hirofumi Ohashi</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Department of Virology II, National Institute of Infectious Diseases, Tokyo</wicri:regionArea>
<placeName><settlement type="city">Tokyo</settlement>
<region type="région">Région de Kantō</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Department of Applied Biological Science, Tokyo University of Science, Tokyo, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Department of Applied Biological Science, Tokyo University of Science, Tokyo</wicri:regionArea>
<placeName><settlement type="city">Tokyo</settlement>
<region type="région">Région de Kantō</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Saso, Wakana" sort="Saso, Wakana" uniqKey="Saso W" first="Wakana" last="Saso">Wakana Saso</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Department of Virology II, National Institute of Infectious Diseases, Tokyo</wicri:regionArea>
<placeName><settlement type="city">Tokyo</settlement>
<region type="région">Région de Kantō</region>
</placeName>
</affiliation>
<affiliation wicri:level="4"><nlm:affiliation>The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>The Institute of Medical Science, The University of Tokyo, Tokyo</wicri:regionArea>
<placeName><settlement type="city">Tokyo</settlement>
<region type="région">Région de Kantō</region>
</placeName>
<orgName type="university">Université de Tokyo</orgName>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>AIDS Research Center, National Institute of Infectious Diseases, Tokyo</wicri:regionArea>
<placeName><settlement type="city">Tokyo</settlement>
<region type="région">Région de Kantō</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Tanaka, Tomohiro" sort="Tanaka, Tomohiro" uniqKey="Tanaka T" first="Tomohiro" last="Tanaka">Tomohiro Tanaka</name>
<affiliation wicri:level="3"><nlm:affiliation>Faculty of Pharmaceutical Sciences, Tokyo University of Science, Tokyo, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Faculty of Pharmaceutical Sciences, Tokyo University of Science, Tokyo</wicri:regionArea>
<placeName><settlement type="city">Tokyo</settlement>
<region type="région">Région de Kantō</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Aoki, Shin" sort="Aoki, Shin" uniqKey="Aoki S" first="Shin" last="Aoki">Shin Aoki</name>
<affiliation wicri:level="3"><nlm:affiliation>Research Institute for Science and Technology, Tokyo University of Science, Tokyo, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Research Institute for Science and Technology, Tokyo University of Science, Tokyo</wicri:regionArea>
<placeName><settlement type="city">Tokyo</settlement>
<region type="région">Région de Kantō</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Kuramochi, Kouji" sort="Kuramochi, Kouji" uniqKey="Kuramochi K" first="Kouji" last="Kuramochi">Kouji Kuramochi</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Applied Biological Science, Tokyo University of Science, Tokyo, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Department of Applied Biological Science, Tokyo University of Science, Tokyo</wicri:regionArea>
<placeName><settlement type="city">Tokyo</settlement>
<region type="région">Région de Kantō</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Iwami, Shingo" sort="Iwami, Shingo" uniqKey="Iwami S" first="Shingo" last="Iwami">Shingo Iwami</name>
<affiliation wicri:level="1"><nlm:affiliation>Interdisciplinary Biology Laboratory (iBLab), Division of Biological Science, Graduate School of Science, Nagoya University, Nagoya, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Interdisciplinary Biology Laboratory (iBLab), Division of Biological Science, Graduate School of Science, Nagoya University, Nagoya</wicri:regionArea>
<wicri:noRegion>Nagoya</wicri:noRegion>
</affiliation>
<affiliation wicri:level="4"><nlm:affiliation>Department of Biology, Faculty of Sciences, Kyushu University, Fukuoka, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Department of Biology, Faculty of Sciences, Kyushu University, Fukuoka</wicri:regionArea>
<orgName type="university">Université de Kyūshū</orgName>
<placeName><settlement type="city">Fukuoka</settlement>
<region type="province">Kyūshū</region>
<region type="prefecture">Préfecture de Fukuoka</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>MIRAI, JST, Saitama, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>MIRAI, JST, Saitama</wicri:regionArea>
<wicri:noRegion>Saitama</wicri:noRegion>
</affiliation>
<affiliation wicri:level="4"><nlm:affiliation>Institute of Mathematics for Industry, Kyushu University, Fukuoka, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Institute of Mathematics for Industry, Kyushu University, Fukuoka</wicri:regionArea>
<orgName type="university">Université de Kyūshū</orgName>
<placeName><settlement type="city">Fukuoka</settlement>
<region type="province">Kyūshū</region>
<region type="prefecture">Préfecture de Fukuoka</region>
</placeName>
</affiliation>
<affiliation wicri:level="4"><nlm:affiliation>Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University, Kyoto, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University, Kyoto</wicri:regionArea>
<orgName type="university">Université de Kyoto</orgName>
<placeName><settlement type="city">Kyoto</settlement>
<region type="prefecture">Région du Kansai</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>NEXT-Ganken Program, Japanese Foundation for Cancer Research (JFCR), Tokyo, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>NEXT-Ganken Program, Japanese Foundation for Cancer Research (JFCR), Tokyo</wicri:regionArea>
<placeName><settlement type="city">Tokyo</settlement>
<region type="région">Région de Kantō</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Science Groove Inc., Fukuoka, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Science Groove Inc., Fukuoka</wicri:regionArea>
<wicri:noRegion>Fukuoka</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Takahashi, Yoshimasa" sort="Takahashi, Yoshimasa" uniqKey="Takahashi Y" first="Yoshimasa" last="Takahashi">Yoshimasa Takahashi</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Immunology, National Institute of Infectious Diseases, Tokyo, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Department of Immunology, National Institute of Infectious Diseases, Tokyo</wicri:regionArea>
<placeName><settlement type="city">Tokyo</settlement>
<region type="région">Région de Kantō</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo</wicri:regionArea>
<placeName><settlement type="city">Tokyo</settlement>
<region type="région">Région de Kantō</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Suzuki, Tadaki" sort="Suzuki, Tadaki" uniqKey="Suzuki T" first="Tadaki" last="Suzuki">Tadaki Suzuki</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Department of Pathology, National Institute of Infectious Diseases, Tokyo</wicri:regionArea>
<placeName><settlement type="city">Tokyo</settlement>
<region type="région">Région de Kantō</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Muramatsu, Masamichi" sort="Muramatsu, Masamichi" uniqKey="Muramatsu M" first="Masamichi" last="Muramatsu">Masamichi Muramatsu</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Department of Virology II, National Institute of Infectious Diseases, Tokyo</wicri:regionArea>
<placeName><settlement type="city">Tokyo</settlement>
<region type="région">Région de Kantō</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Takeda, Makoto" sort="Takeda, Makoto" uniqKey="Takeda M" first="Makoto" last="Takeda">Makoto Takeda</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Virology III, National Institute of Infectious Diseases, Tokyo, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Department of Virology III, National Institute of Infectious Diseases, Tokyo</wicri:regionArea>
<placeName><settlement type="city">Tokyo</settlement>
<region type="région">Région de Kantō</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Wakita, Takaji" sort="Wakita, Takaji" uniqKey="Wakita T" first="Takaji" last="Wakita">Takaji Wakita</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Department of Virology II, National Institute of Infectious Diseases, Tokyo</wicri:regionArea>
<placeName><settlement type="city">Tokyo</settlement>
<region type="région">Région de Kantō</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Watashi, Koichi" sort="Watashi, Koichi" uniqKey="Watashi K" first="Koichi" last="Watashi">Koichi Watashi</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Department of Virology II, National Institute of Infectious Diseases, Tokyo</wicri:regionArea>
<placeName><settlement type="city">Tokyo</settlement>
<region type="région">Région de Kantō</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Department of Applied Biological Science, Tokyo University of Science, Tokyo, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Department of Applied Biological Science, Tokyo University of Science, Tokyo</wicri:regionArea>
<placeName><settlement type="city">Tokyo</settlement>
<region type="région">Région de Kantō</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>MIRAI, JST, Saitama, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>MIRAI, JST, Saitama</wicri:regionArea>
<wicri:noRegion>Saitama</wicri:noRegion>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo</wicri:regionArea>
<placeName><settlement type="city">Tokyo</settlement>
<region type="région">Région de Kantō</region>
</placeName>
</affiliation>
<affiliation wicri:level="4"><nlm:affiliation>Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto</wicri:regionArea>
<orgName type="university">Université de Kyoto</orgName>
<placeName><settlement type="city">Kyoto</settlement>
<region type="prefecture">Région du Kansai</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">Frontiers in microbiology</title>
<idno type="ISSN">1664-302X</idno>
<imprint><date when="2021" type="published">2021</date>
</imprint>
</series>
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<front><div type="abstract" xml:lang="en">Coronavirus disease 2019 (COVID-19) has caused serious public health, social, and economic damage worldwide and effective drugs that prevent or cure COVID-19 are urgently needed. Approved drugs including Hydroxychloroquine, Remdesivir or Interferon were reported to inhibit the infection or propagation of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), however, their clinical efficacies have not yet been well demonstrated. To identify drugs with higher antiviral potency, we screened approved anti-parasitic/anti-protozoal drugs and identified an anti-malarial drug, Mefloquine, which showed the highest anti-SARS-CoV-2 activity among the tested compounds. Mefloquine showed higher anti-SARS-CoV-2 activity than Hydroxychloroquine in VeroE6/TMPRSS2 and Calu-3 cells, with IC<sub>50</sub>
= 1.28 μM, IC<sub>90</sub>
= 2.31 μM, and IC<sub>99</sub>
= 4.39 μM in VeroE6/TMPRSS2 cells. Mefloquine inhibited viral entry after viral attachment to the target cell. Combined treatment with Mefloquine and Nelfinavir, a replication inhibitor, showed synergistic antiviral activity. Our mathematical modeling based on the drug concentration in the lung predicted that Mefloquine administration at a standard treatment dosage could decline viral dynamics in patients, reduce cumulative viral load to 7% and shorten the time until virus elimination by 6.1 days. These data cumulatively underscore Mefloquine as an anti-SARS-CoV-2 entry inhibitor.</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM"><PMID Version="1">33995308</PMID>
<DateRevised><Year>2021</Year>
<Month>05</Month>
<Day>18</Day>
</DateRevised>
<Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Print">1664-302X</ISSN>
<JournalIssue CitedMedium="Print"><Volume>12</Volume>
<PubDate><Year>2021</Year>
</PubDate>
</JournalIssue>
<Title>Frontiers in microbiology</Title>
<ISOAbbreviation>Front Microbiol</ISOAbbreviation>
</Journal>
<ArticleTitle>Mefloquine, a Potent Anti-severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2) Drug as an Entry Inhibitor <i>in vitro</i>
.</ArticleTitle>
<Pagination><MedlinePgn>651403</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.3389/fmicb.2021.651403</ELocationID>
<Abstract><AbstractText>Coronavirus disease 2019 (COVID-19) has caused serious public health, social, and economic damage worldwide and effective drugs that prevent or cure COVID-19 are urgently needed. Approved drugs including Hydroxychloroquine, Remdesivir or Interferon were reported to inhibit the infection or propagation of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), however, their clinical efficacies have not yet been well demonstrated. To identify drugs with higher antiviral potency, we screened approved anti-parasitic/anti-protozoal drugs and identified an anti-malarial drug, Mefloquine, which showed the highest anti-SARS-CoV-2 activity among the tested compounds. Mefloquine showed higher anti-SARS-CoV-2 activity than Hydroxychloroquine in VeroE6/TMPRSS2 and Calu-3 cells, with IC<sub>50</sub>
= 1.28 μM, IC<sub>90</sub>
= 2.31 μM, and IC<sub>99</sub>
= 4.39 μM in VeroE6/TMPRSS2 cells. Mefloquine inhibited viral entry after viral attachment to the target cell. Combined treatment with Mefloquine and Nelfinavir, a replication inhibitor, showed synergistic antiviral activity. Our mathematical modeling based on the drug concentration in the lung predicted that Mefloquine administration at a standard treatment dosage could decline viral dynamics in patients, reduce cumulative viral load to 7% and shorten the time until virus elimination by 6.1 days. These data cumulatively underscore Mefloquine as an anti-SARS-CoV-2 entry inhibitor.</AbstractText>
<CopyrightInformation>Copyright © 2021 Shionoya, Yamasaki, Iwanami, Ito, Fukushi, Ohashi, Saso, Tanaka, Aoki, Kuramochi, Iwami, Takahashi, Suzuki, Muramatsu, Takeda, Wakita and Watashi.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Shionoya</LastName>
<ForeName>Kaho</ForeName>
<Initials>K</Initials>
<AffiliationInfo><Affiliation>Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Applied Biological Science, Tokyo University of Science, Tokyo, Japan.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Yamasaki</LastName>
<ForeName>Masako</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Applied Biological Science, Tokyo University of Science, Tokyo, Japan.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Iwanami</LastName>
<ForeName>Shoya</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Interdisciplinary Biology Laboratory (iBLab), Division of Biological Science, Graduate School of Science, Nagoya University, Nagoya, Japan.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Biology, Faculty of Sciences, Kyushu University, Fukuoka, Japan.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ito</LastName>
<ForeName>Yusuke</ForeName>
<Initials>Y</Initials>
<AffiliationInfo><Affiliation>Department of Biology, Faculty of Sciences, Kyushu University, Fukuoka, Japan.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Fukushi</LastName>
<ForeName>Shuetsu</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Department of Virology I, National Institute of Infectious Diseases, Tokyo, Japan.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ohashi</LastName>
<ForeName>Hirofumi</ForeName>
<Initials>H</Initials>
<AffiliationInfo><Affiliation>Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Applied Biological Science, Tokyo University of Science, Tokyo, Japan.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Saso</LastName>
<ForeName>Wakana</ForeName>
<Initials>W</Initials>
<AffiliationInfo><Affiliation>Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Tanaka</LastName>
<ForeName>Tomohiro</ForeName>
<Initials>T</Initials>
<AffiliationInfo><Affiliation>Faculty of Pharmaceutical Sciences, Tokyo University of Science, Tokyo, Japan.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Aoki</LastName>
<ForeName>Shin</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Research Institute for Science and Technology, Tokyo University of Science, Tokyo, Japan.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Kuramochi</LastName>
<ForeName>Kouji</ForeName>
<Initials>K</Initials>
<AffiliationInfo><Affiliation>Department of Applied Biological Science, Tokyo University of Science, Tokyo, Japan.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Iwami</LastName>
<ForeName>Shingo</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Interdisciplinary Biology Laboratory (iBLab), Division of Biological Science, Graduate School of Science, Nagoya University, Nagoya, Japan.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Biology, Faculty of Sciences, Kyushu University, Fukuoka, Japan.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>MIRAI, JST, Saitama, Japan.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Institute of Mathematics for Industry, Kyushu University, Fukuoka, Japan.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University, Kyoto, Japan.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>NEXT-Ganken Program, Japanese Foundation for Cancer Research (JFCR), Tokyo, Japan.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Science Groove Inc., Fukuoka, Japan.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Takahashi</LastName>
<ForeName>Yoshimasa</ForeName>
<Initials>Y</Initials>
<AffiliationInfo><Affiliation>Department of Immunology, National Institute of Infectious Diseases, Tokyo, Japan.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo, Japan.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Suzuki</LastName>
<ForeName>Tadaki</ForeName>
<Initials>T</Initials>
<AffiliationInfo><Affiliation>Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Muramatsu</LastName>
<ForeName>Masamichi</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Takeda</LastName>
<ForeName>Makoto</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Department of Virology III, National Institute of Infectious Diseases, Tokyo, Japan.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Wakita</LastName>
<ForeName>Takaji</ForeName>
<Initials>T</Initials>
<AffiliationInfo><Affiliation>Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Watashi</LastName>
<ForeName>Koichi</ForeName>
<Initials>K</Initials>
<AffiliationInfo><Affiliation>Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Applied Biological Science, Tokyo University of Science, Tokyo, Japan.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>MIRAI, JST, Saitama, Japan.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo, Japan.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2021</Year>
<Month>04</Month>
<Day>30</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>Switzerland</Country>
<MedlineTA>Front Microbiol</MedlineTA>
<NlmUniqueID>101548977</NlmUniqueID>
<ISSNLinking>1664-302X</ISSNLinking>
</MedlineJournalInfo>
<KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">COVID-19</Keyword>
<Keyword MajorTopicYN="N">SARS-CoV-2</Keyword>
<Keyword MajorTopicYN="N">coronavirus</Keyword>
<Keyword MajorTopicYN="N">malaria</Keyword>
<Keyword MajorTopicYN="N">mefloquine</Keyword>
<Keyword MajorTopicYN="N">repurposing</Keyword>
<Keyword MajorTopicYN="N">severe acute respiratory syndrome-related coronavirus 2</Keyword>
</KeywordList>
<CoiStatement>SI was employed by the Science Groove Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</CoiStatement>
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<affiliations><list><country><li>Japon</li>
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<region><li>Kyūshū</li>
<li>Préfecture de Fukuoka</li>
<li>Région de Kantō</li>
<li>Région du Kansai</li>
</region>
<settlement><li>Fukuoka</li>
<li>Kyoto</li>
<li>Tokyo</li>
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<orgName><li>Université de Kyoto</li>
<li>Université de Kyūshū</li>
<li>Université de Tokyo</li>
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<tree><country name="Japon"><region name="Région de Kantō"><name sortKey="Shionoya, Kaho" sort="Shionoya, Kaho" uniqKey="Shionoya K" first="Kaho" last="Shionoya">Kaho Shionoya</name>
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<name sortKey="Iwami, Shingo" sort="Iwami, Shingo" uniqKey="Iwami S" first="Shingo" last="Iwami">Shingo Iwami</name>
<name sortKey="Iwami, Shingo" sort="Iwami, Shingo" uniqKey="Iwami S" first="Shingo" last="Iwami">Shingo Iwami</name>
<name sortKey="Iwami, Shingo" sort="Iwami, Shingo" uniqKey="Iwami S" first="Shingo" last="Iwami">Shingo Iwami</name>
<name sortKey="Iwanami, Shoya" sort="Iwanami, Shoya" uniqKey="Iwanami S" first="Shoya" last="Iwanami">Shoya Iwanami</name>
<name sortKey="Iwanami, Shoya" sort="Iwanami, Shoya" uniqKey="Iwanami S" first="Shoya" last="Iwanami">Shoya Iwanami</name>
<name sortKey="Kuramochi, Kouji" sort="Kuramochi, Kouji" uniqKey="Kuramochi K" first="Kouji" last="Kuramochi">Kouji Kuramochi</name>
<name sortKey="Muramatsu, Masamichi" sort="Muramatsu, Masamichi" uniqKey="Muramatsu M" first="Masamichi" last="Muramatsu">Masamichi Muramatsu</name>
<name sortKey="Ohashi, Hirofumi" sort="Ohashi, Hirofumi" uniqKey="Ohashi H" first="Hirofumi" last="Ohashi">Hirofumi Ohashi</name>
<name sortKey="Ohashi, Hirofumi" sort="Ohashi, Hirofumi" uniqKey="Ohashi H" first="Hirofumi" last="Ohashi">Hirofumi Ohashi</name>
<name sortKey="Saso, Wakana" sort="Saso, Wakana" uniqKey="Saso W" first="Wakana" last="Saso">Wakana Saso</name>
<name sortKey="Saso, Wakana" sort="Saso, Wakana" uniqKey="Saso W" first="Wakana" last="Saso">Wakana Saso</name>
<name sortKey="Saso, Wakana" sort="Saso, Wakana" uniqKey="Saso W" first="Wakana" last="Saso">Wakana Saso</name>
<name sortKey="Shionoya, Kaho" sort="Shionoya, Kaho" uniqKey="Shionoya K" first="Kaho" last="Shionoya">Kaho Shionoya</name>
<name sortKey="Suzuki, Tadaki" sort="Suzuki, Tadaki" uniqKey="Suzuki T" first="Tadaki" last="Suzuki">Tadaki Suzuki</name>
<name sortKey="Takahashi, Yoshimasa" sort="Takahashi, Yoshimasa" uniqKey="Takahashi Y" first="Yoshimasa" last="Takahashi">Yoshimasa Takahashi</name>
<name sortKey="Takahashi, Yoshimasa" sort="Takahashi, Yoshimasa" uniqKey="Takahashi Y" first="Yoshimasa" last="Takahashi">Yoshimasa Takahashi</name>
<name sortKey="Takeda, Makoto" sort="Takeda, Makoto" uniqKey="Takeda M" first="Makoto" last="Takeda">Makoto Takeda</name>
<name sortKey="Tanaka, Tomohiro" sort="Tanaka, Tomohiro" uniqKey="Tanaka T" first="Tomohiro" last="Tanaka">Tomohiro Tanaka</name>
<name sortKey="Wakita, Takaji" sort="Wakita, Takaji" uniqKey="Wakita T" first="Takaji" last="Wakita">Takaji Wakita</name>
<name sortKey="Watashi, Koichi" sort="Watashi, Koichi" uniqKey="Watashi K" first="Koichi" last="Watashi">Koichi Watashi</name>
<name sortKey="Watashi, Koichi" sort="Watashi, Koichi" uniqKey="Watashi K" first="Koichi" last="Watashi">Koichi Watashi</name>
<name sortKey="Watashi, Koichi" sort="Watashi, Koichi" uniqKey="Watashi K" first="Koichi" last="Watashi">Koichi Watashi</name>
<name sortKey="Watashi, Koichi" sort="Watashi, Koichi" uniqKey="Watashi K" first="Koichi" last="Watashi">Koichi Watashi</name>
<name sortKey="Watashi, Koichi" sort="Watashi, Koichi" uniqKey="Watashi K" first="Koichi" last="Watashi">Koichi Watashi</name>
<name sortKey="Yamasaki, Masako" sort="Yamasaki, Masako" uniqKey="Yamasaki M" first="Masako" last="Yamasaki">Masako Yamasaki</name>
<name sortKey="Yamasaki, Masako" sort="Yamasaki, Masako" uniqKey="Yamasaki M" first="Masako" last="Yamasaki">Masako Yamasaki</name>
</country>
</tree>
</affiliations>
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