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
Links toward previous steps (curation, corpus...)
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Mefloquine, a Potent Anti-severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2) Drug as an Entry Inhibitor <i>in vitro</i>.</title><author><name sortKey="Shionoya, Kaho" sort="Shionoya, Kaho" uniqKey="Shionoya K" first="Kaho" last="Shionoya">Kaho Shionoya</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="Yamasaki, Masako" sort="Yamasaki, Masako" uniqKey="Yamasaki M" first="Masako" last="Yamasaki">Masako Yamasaki</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="Iwanami, Shoya" sort="Iwanami, Shoya" uniqKey="Iwanami S" first="Shoya" last="Iwanami">Shoya Iwanami</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></author><author><name sortKey="Ito, Yusuke" sort="Ito, Yusuke" uniqKey="Ito Y" first="Yusuke" last="Ito">Yusuke Ito</name><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></author><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></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2021">2021</date><idno type="RBID">pubmed:33995308</idno><idno type="pmid">33995308</idno><idno type="doi">10.3389/fmicb.2021.651403</idno><idno type="pmc">PMC8119653</idno><idno type="wicri:Area/Main/Corpus">000015</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000015</idno><idno type="wicri:Area/Main/Curation">000015</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000015</idno><idno type="wicri:Area/Main/Exploration">000015</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Mefloquine, a Potent Anti-severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2) Drug as an Entry Inhibitor <i>in vitro</i>.</title><author><name sortKey="Shionoya, Kaho" sort="Shionoya, Kaho" uniqKey="Shionoya K" first="Kaho" last="Shionoya">Kaho Shionoya</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="Yamasaki, Masako" sort="Yamasaki, Masako" uniqKey="Yamasaki M" first="Masako" last="Yamasaki">Masako Yamasaki</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="Iwanami, Shoya" sort="Iwanami, Shoya" uniqKey="Iwanami S" first="Shoya" last="Iwanami">Shoya Iwanami</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></author><author><name sortKey="Ito, Yusuke" sort="Ito, Yusuke" uniqKey="Ito Y" first="Yusuke" last="Ito">Yusuke Ito</name><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></author><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></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><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></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2021</Year><Month>01</Month><Day>09</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2021</Year><Month>04</Month><Day>06</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2021</Year><Month>5</Month><Day>17</Day><Hour>6</Hour><Minute>3</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2021</Year><Month>5</Month><Day>18</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2021</Year><Month>5</Month><Day>18</Day><Hour>6</Hour><Minute>1</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">33995308</ArticleId><ArticleId IdType="doi">10.3389/fmicb.2021.651403</ArticleId><ArticleId IdType="pmc">PMC8119653</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>J Virol. 2020 Oct 14;94(21):</Citation><ArticleIdList><ArticleId IdType="pubmed">32817221</ArticleId></ArticleIdList></Reference><Reference><Citation>Int J Mol Sci. 2020 Aug 18;21(16):</Citation><ArticleIdList><ArticleId IdType="pubmed">32824753</ArticleId></ArticleIdList></Reference><Reference><Citation>Clin Pharmacokinet. 1990 Oct;19(4):264-79</Citation><ArticleIdList><ArticleId IdType="pubmed">2208897</ArticleId></ArticleIdList></Reference><Reference><Citation>J Chem Inf Comput Sci. 1987 Feb;27(1):21-35</Citation><ArticleIdList><ArticleId IdType="pubmed">3558506</ArticleId></ArticleIdList></Reference><Reference><Citation>Nat Med. 2008 Jul;14(7):762-6</Citation><ArticleIdList><ArticleId IdType="pubmed">18552857</ArticleId></ArticleIdList></Reference><Reference><Citation>JCI Insight. 2020 Oct 2;5(19):</Citation><ArticleIdList><ArticleId IdType="pubmed">32841215</ArticleId></ArticleIdList></Reference><Reference><Citation>Biochem Biophys Res Commun. 2004 Jun 4;318(3):719-25</Citation><ArticleIdList><ArticleId IdType="pubmed">15144898</ArticleId></ArticleIdList></Reference><Reference><Citation>J Antimicrob Chemother. 2015;70(6):1608-21</Citation><ArticleIdList><ArticleId IdType="pubmed">25693996</ArticleId></ArticleIdList></Reference><Reference><Citation>BMJ. 2020 May 14;369:m1849</Citation><ArticleIdList><ArticleId IdType="pubmed">32409561</ArticleId></ArticleIdList></Reference><Reference><Citation>Proc Natl Acad Sci U S A. 2017 Feb 21;114(8):1922-1927</Citation><ArticleIdList><ArticleId IdType="pubmed">28174263</ArticleId></ArticleIdList></Reference><Reference><Citation>Antimicrob Agents Chemother. 2020 Jun 23;64(7):</Citation><ArticleIdList><ArticleId IdType="pubmed">32366720</ArticleId></ArticleIdList></Reference><Reference><Citation>J Virol. 2021 Jan 13;95(3):</Citation><ArticleIdList><ArticleId IdType="pubmed">33173010</ArticleId></ArticleIdList></Reference><Reference><Citation>Euro Surveill. 2020 Jan;25(3):</Citation><ArticleIdList><ArticleId IdType="pubmed">31992387</ArticleId></ArticleIdList></Reference><Reference><Citation>Clin Pharmacol Ther. 1979 Sep;26(3):372-9</Citation><ArticleIdList><ArticleId IdType="pubmed">466930</ArticleId></ArticleIdList></Reference><Reference><Citation>Cell Res. 2020 Mar;30(3):269-271</Citation><ArticleIdList><ArticleId IdType="pubmed">32020029</ArticleId></ArticleIdList></Reference><Reference><Citation>Chin Med J (Engl). 2020 May 5;133(9):1051-1056</Citation><ArticleIdList><ArticleId IdType="pubmed">32149769</ArticleId></ArticleIdList></Reference><Reference><Citation>Parasite. 2014;21:61</Citation><ArticleIdList><ArticleId IdType="pubmed">25402734</ArticleId></ArticleIdList></Reference><Reference><Citation>Viruses. 2021 Apr 09;13(4):</Citation><ArticleIdList><ArticleId IdType="pubmed">33918958</ArticleId></ArticleIdList></Reference><Reference><Citation>Science. 2020 Jul 3;369(6499):77-81</Citation><ArticleIdList><ArticleId IdType="pubmed">32376603</ArticleId></ArticleIdList></Reference><Reference><Citation>Cell. 2020 Aug 6;182(3):744-753.e4</Citation><ArticleIdList><ArticleId IdType="pubmed">32553273</ArticleId></ArticleIdList></Reference><Reference><Citation>mBio. 2020 May 22;11(3):</Citation><ArticleIdList><ArticleId IdType="pubmed">32444382</ArticleId></ArticleIdList></Reference><Reference><Citation>Nat Commun. 2020 Jul 8;11(1):3496</Citation><ArticleIdList><ArticleId IdType="pubmed">32641684</ArticleId></ArticleIdList></Reference><Reference><Citation>Biochem Biophys Res Commun. 2004 Jul 9;319(4):1228-34</Citation><ArticleIdList><ArticleId IdType="pubmed">15194498</ArticleId></ArticleIdList></Reference><Reference><Citation>J Antimicrob Chemother. 2012 Aug;67(8):1884-94</Citation><ArticleIdList><ArticleId IdType="pubmed">22535622</ArticleId></ArticleIdList></Reference><Reference><Citation>Proc Natl Acad Sci U S A. 2020 Mar 31;117(13):7001-7003</Citation><ArticleIdList><ArticleId IdType="pubmed">32165541</ArticleId></ArticleIdList></Reference><Reference><Citation>Cell Discov. 2020 Mar 18;6:16</Citation><ArticleIdList><ArticleId IdType="pubmed">32194981</ArticleId></ArticleIdList></Reference><Reference><Citation>Forensic Sci Int. 1994 Sep 6;68(1):29-32</Citation><ArticleIdList><ArticleId IdType="pubmed">7959478</ArticleId></ArticleIdList></Reference><Reference><Citation>Br J Clin Pharmacol. 1993 Nov;36(5):405-11</Citation><ArticleIdList><ArticleId IdType="pubmed">12959287</ArticleId></ArticleIdList></Reference><Reference><Citation>J Crit Care. 2020 Oct;59:176-190</Citation><ArticleIdList><ArticleId IdType="pubmed">32683212</ArticleId></ArticleIdList></Reference><Reference><Citation>Nature. 2020 Jul;583(7818):834-838</Citation><ArticleIdList><ArticleId IdType="pubmed">32408338</ArticleId></ArticleIdList></Reference><Reference><Citation>Science. 2020 Sep 25;369(6511):1603-1607</Citation><ArticleIdList><ArticleId IdType="pubmed">32732280</ArticleId></ArticleIdList></Reference><Reference><Citation>JAMA. 2020 Jun 23;323(24):2493-2502</Citation><ArticleIdList><ArticleId IdType="pubmed">32392282</ArticleId></ArticleIdList></Reference><Reference><Citation>Science. 2020 Aug 21;369(6506):956-963</Citation><ArticleIdList><ArticleId IdType="pubmed">32540903</ArticleId></ArticleIdList></Reference><Reference><Citation>Br J Pharmacol. 2021 Feb;178(3):626-635</Citation><ArticleIdList><ArticleId IdType="pubmed">33125711</ArticleId></ArticleIdList></Reference><Reference><Citation>Sci Rep. 2019 Dec 27;9(1):20199</Citation><ArticleIdList><ArticleId IdType="pubmed">31882748</ArticleId></ArticleIdList></Reference><Reference><Citation>Proc Natl Acad Sci U S A. 2020 Jul 14;117(28):16587-16595</Citation><ArticleIdList><ArticleId IdType="pubmed">32571934</ArticleId></ArticleIdList></Reference><Reference><Citation>J Virol. 2019 May 15;93(11):</Citation><ArticleIdList><ArticleId IdType="pubmed">30894466</ArticleId></ArticleIdList></Reference><Reference><Citation>Antimicrob Agents Chemother. 2009 Apr;53(4):1468-75</Citation><ArticleIdList><ArticleId IdType="pubmed">19188392</ArticleId></ArticleIdList></Reference><Reference><Citation>J Gen Virol. 2005 Aug;86(Pt 8):2269-2274</Citation><ArticleIdList><ArticleId IdType="pubmed">16033974</ArticleId></ArticleIdList></Reference><Reference><Citation>PLoS One. 2019 Apr 23;14(4):e0215822</Citation><ArticleIdList><ArticleId IdType="pubmed">31013314</ArticleId></ArticleIdList></Reference><Reference><Citation>Antimicrob Agents Chemother. 2009 Aug;53(8):3416-21</Citation><ArticleIdList><ArticleId IdType="pubmed">19506054</ArticleId></ArticleIdList></Reference><Reference><Citation>Travel Med Infect Dis. 2020 Sep - Oct;37:101873</Citation><ArticleIdList><ArticleId IdType="pubmed">32916297</ArticleId></ArticleIdList></Reference><Reference><Citation>Cell Host Microbe. 2020 May 13;27(5):704-709.e2</Citation><ArticleIdList><ArticleId IdType="pubmed">32259477</ArticleId></ArticleIdList></Reference><Reference><Citation>Cell. 2020 Jul 9;182(1):50-58.e8</Citation><ArticleIdList><ArticleId IdType="pubmed">32516571</ArticleId></ArticleIdList></Reference><Reference><Citation>Science. 2020 May 29;368(6494):1012-1015</Citation><ArticleIdList><ArticleId IdType="pubmed">32303590</ArticleId></ArticleIdList></Reference><Reference><Citation>Nature. 2020 Jul;583(7818):830-833</Citation><ArticleIdList><ArticleId IdType="pubmed">32380511</ArticleId></ArticleIdList></Reference><Reference><Citation>iScience. 2021 Apr 23;24(4):102367</Citation><ArticleIdList><ArticleId IdType="pubmed">33817567</ArticleId></ArticleIdList></Reference><Reference><Citation>J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Jan 1;1072:320-327</Citation><ArticleIdList><ArticleId IdType="pubmed">29207305</ArticleId></ArticleIdList></Reference><Reference><Citation>Science. 2020 May 29;368(6494):1016-1020</Citation><ArticleIdList><ArticleId IdType="pubmed">32269068</ArticleId></ArticleIdList></Reference><Reference><Citation>Cell. 2020 Aug 6;182(3):734-743.e5</Citation><ArticleIdList><ArticleId IdType="pubmed">32643603</ArticleId></ArticleIdList></Reference><Reference><Citation>N Engl J Med. 2020 Jun 18;382(25):2411-2418</Citation><ArticleIdList><ArticleId IdType="pubmed">32379955</ArticleId></ArticleIdList></Reference><Reference><Citation>J Exp Med. 2003 Mar 3;197(5):633-42</Citation><ArticleIdList><ArticleId IdType="pubmed">12615904</ArticleId></ArticleIdList></Reference><Reference><Citation>Science. 2020 Aug 14;369(6505):806-811</Citation><ArticleIdList><ArticleId IdType="pubmed">32434945</ArticleId></ArticleIdList></Reference><Reference><Citation>Genes Dis. 2020 Dec;7(4):551-557</Citation><ArticleIdList><ArticleId IdType="pubmed">32837985</ArticleId></ArticleIdList></Reference><Reference><Citation>J Biol Chem. 2018 Dec 21;293(51):19559-19571</Citation><ArticleIdList><ArticleId IdType="pubmed">30381393</ArticleId></ArticleIdList></Reference><Reference><Citation>Cell. 2020 Apr 16;181(2):271-280.e8</Citation><ArticleIdList><ArticleId IdType="pubmed">32142651</ArticleId></ArticleIdList></Reference><Reference><Citation>Sci China Life Sci. 2020 Oct;63(10):1515-1521</Citation><ArticleIdList><ArticleId IdType="pubmed">32418114</ArticleId></ArticleIdList></Reference><Reference><Citation>J Virol. 2010 Mar;84(6):2798-807</Citation><ArticleIdList><ArticleId IdType="pubmed">20053738</ArticleId></ArticleIdList></Reference><Reference><Citation>mBio. 2020 Aug 20;11(4):</Citation><ArticleIdList><ArticleId IdType="pubmed">32820005</ArticleId></ArticleIdList></Reference><Reference><Citation>Sci Rep. 2020 Aug 4;10(1):13093</Citation><ArticleIdList><ArticleId IdType="pubmed">32753646</ArticleId></ArticleIdList></Reference><Reference><Citation>Nat Commun. 2020 Aug 26;11(1):4253</Citation><ArticleIdList><ArticleId IdType="pubmed">32848158</ArticleId></ArticleIdList></Reference><Reference><Citation>Nat Immunol. 2020 Nov;21(11):1327-1335</Citation><ArticleIdList><ArticleId IdType="pubmed">32839612</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></pubmed><affiliations><list><country><li>Japon</li></country><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></settlement><orgName><li>Université de Kyoto</li><li>Université de Kyūshū</li><li>Université de Tokyo</li></orgName></list><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></region><name sortKey="Aoki, Shin" sort="Aoki, Shin" uniqKey="Aoki S" first="Shin" last="Aoki">Shin Aoki</name><name sortKey="Fukushi, Shuetsu" sort="Fukushi, Shuetsu" uniqKey="Fukushi S" first="Shuetsu" last="Fukushi">Shuetsu Fukushi</name><name sortKey="Ito, Yusuke" sort="Ito, Yusuke" uniqKey="Ito Y" first="Yusuke" last="Ito">Yusuke Ito</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="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="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></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/CovidChloroV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000341 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000341 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= CovidChloroV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= pubmed:33995308
|texte= Mefloquine, a Potent Anti-severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2) Drug as an Entry Inhibitor in vitro.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:33995308" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a CovidChloroV1
| This area was generated with Dilib version V0.6.38. |  |