Mefloquine, a Potent Anti-severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2) Drug as an Entry Inhibitor in vitro
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 propagati...
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| Format: | Article |
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Frontiers Media S.A.
2021-04-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2021.651403/full |
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| author | Kaho Shionoya Kaho Shionoya Masako Yamasaki Masako Yamasaki Shoya Iwanami Shoya Iwanami Yusuke Ito Shuetsu Fukushi Hirofumi Ohashi Hirofumi Ohashi Wakana Saso Wakana Saso Wakana Saso Tomohiro Tanaka Shin Aoki Kouji Kuramochi Shingo Iwami Shingo Iwami Shingo Iwami Shingo Iwami Shingo Iwami Shingo Iwami Shingo Iwami Yoshimasa Takahashi Yoshimasa Takahashi Tadaki Suzuki Masamichi Muramatsu Makoto Takeda Takaji Wakita Koichi Watashi Koichi Watashi Koichi Watashi Koichi Watashi Koichi Watashi |
| author_facet | Kaho Shionoya Kaho Shionoya Masako Yamasaki Masako Yamasaki Shoya Iwanami Shoya Iwanami Yusuke Ito Shuetsu Fukushi Hirofumi Ohashi Hirofumi Ohashi Wakana Saso Wakana Saso Wakana Saso Tomohiro Tanaka Shin Aoki Kouji Kuramochi Shingo Iwami Shingo Iwami Shingo Iwami Shingo Iwami Shingo Iwami Shingo Iwami Shingo Iwami Yoshimasa Takahashi Yoshimasa Takahashi Tadaki Suzuki Masamichi Muramatsu Makoto Takeda Takaji Wakita Koichi Watashi Koichi Watashi Koichi Watashi Koichi Watashi Koichi Watashi |
| author_sort | Kaho Shionoya |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-17T22:20:58Z |
| format | Article |
| id | doaj.art-04c84a66c3fc4820b9e215e12bd83143 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-17T22:20:58Z |
| publishDate | 2021-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-04c84a66c3fc4820b9e215e12bd831432022-12-21T21:30:28ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2021-04-011210.3389/fmicb.2021.651403651403Mefloquine, a Potent Anti-severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2) Drug as an Entry Inhibitor in vitroKaho Shionoya0Kaho Shionoya1Masako Yamasaki2Masako Yamasaki3Shoya Iwanami4Shoya Iwanami5Yusuke Ito6Shuetsu Fukushi7Hirofumi Ohashi8Hirofumi Ohashi9Wakana Saso10Wakana Saso11Wakana Saso12Tomohiro Tanaka13Shin Aoki14Kouji Kuramochi15Shingo Iwami16Shingo Iwami17Shingo Iwami18Shingo Iwami19Shingo Iwami20Shingo Iwami21Shingo Iwami22Yoshimasa Takahashi23Yoshimasa Takahashi24Tadaki Suzuki25Masamichi Muramatsu26Makoto Takeda27Takaji Wakita28Koichi Watashi29Koichi Watashi30Koichi Watashi31Koichi Watashi32Koichi Watashi33Department of Virology II, National Institute of Infectious Diseases, Tokyo, JapanDepartment of Applied Biological Science, Tokyo University of Science, Tokyo, JapanDepartment of Virology II, National Institute of Infectious Diseases, Tokyo, JapanDepartment of Applied Biological Science, Tokyo University of Science, Tokyo, JapanInterdisciplinary Biology Laboratory (iBLab), Division of Biological Science, Graduate School of Science, Nagoya University, Nagoya, JapanDepartment of Biology, Faculty of Sciences, Kyushu University, Fukuoka, JapanDepartment of Biology, Faculty of Sciences, Kyushu University, Fukuoka, JapanDepartment of Virology I, National Institute of Infectious Diseases, Tokyo, JapanDepartment of Virology II, National Institute of Infectious Diseases, Tokyo, JapanDepartment of Applied Biological Science, Tokyo University of Science, Tokyo, JapanDepartment of Virology II, National Institute of Infectious Diseases, Tokyo, JapanThe Institute of Medical Science, The University of Tokyo, Tokyo, JapanAIDS Research Center, National Institute of Infectious Diseases, Tokyo, JapanFaculty of Pharmaceutical Sciences, Tokyo University of Science, Tokyo, JapanResearch Institute for Science and Technology, Tokyo University of Science, Tokyo, JapanDepartment of Applied Biological Science, Tokyo University of Science, Tokyo, JapanInterdisciplinary Biology Laboratory (iBLab), Division of Biological Science, Graduate School of Science, Nagoya University, Nagoya, JapanDepartment of Biology, Faculty of Sciences, Kyushu University, Fukuoka, Japan0MIRAI, JST, Saitama, Japan1Institute of Mathematics for Industry, Kyushu University, Fukuoka, Japan2Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University, Kyoto, Japan3NEXT-Ganken Program, Japanese Foundation for Cancer Research (JFCR), Tokyo, Japan4Science Groove Inc., Fukuoka, Japan5Department of Immunology, National Institute of Infectious Diseases, Tokyo, Japan6Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo, Japan7Department of Pathology, National Institute of Infectious Diseases, Tokyo, JapanDepartment of Virology II, National Institute of Infectious Diseases, Tokyo, Japan8Department of Virology III, National Institute of Infectious Diseases, Tokyo, JapanDepartment of Virology II, National Institute of Infectious Diseases, Tokyo, JapanDepartment of Virology II, National Institute of Infectious Diseases, Tokyo, JapanDepartment of Applied Biological Science, Tokyo University of Science, Tokyo, Japan0MIRAI, JST, Saitama, Japan6Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo, Japan9Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, JapanCoronavirus 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.https://www.frontiersin.org/articles/10.3389/fmicb.2021.651403/fullCOVID-19severe acute respiratory syndrome-related coronavirus 2SARS-CoV-2repurposingmalariamefloquine |
| spellingShingle | Kaho Shionoya Kaho Shionoya Masako Yamasaki Masako Yamasaki Shoya Iwanami Shoya Iwanami Yusuke Ito Shuetsu Fukushi Hirofumi Ohashi Hirofumi Ohashi Wakana Saso Wakana Saso Wakana Saso Tomohiro Tanaka Shin Aoki Kouji Kuramochi Shingo Iwami Shingo Iwami Shingo Iwami Shingo Iwami Shingo Iwami Shingo Iwami Shingo Iwami Yoshimasa Takahashi Yoshimasa Takahashi Tadaki Suzuki Masamichi Muramatsu Makoto Takeda Takaji Wakita Koichi Watashi Koichi Watashi Koichi Watashi Koichi Watashi Koichi Watashi Mefloquine, a Potent Anti-severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2) Drug as an Entry Inhibitor in vitro Frontiers in Microbiology COVID-19 severe acute respiratory syndrome-related coronavirus 2 SARS-CoV-2 repurposing malaria mefloquine |
| title | Mefloquine, a Potent Anti-severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2) Drug as an Entry Inhibitor in vitro |
| title_full | Mefloquine, a Potent Anti-severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2) Drug as an Entry Inhibitor in vitro |
| title_fullStr | Mefloquine, a Potent Anti-severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2) Drug as an Entry Inhibitor in vitro |
| title_full_unstemmed | Mefloquine, a Potent Anti-severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2) Drug as an Entry Inhibitor in vitro |
| title_short | Mefloquine, a Potent Anti-severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2) Drug as an Entry Inhibitor in vitro |
| title_sort | mefloquine a potent anti severe acute respiratory syndrome related coronavirus 2 sars cov 2 drug as an entry inhibitor in vitro |
| topic | COVID-19 severe acute respiratory syndrome-related coronavirus 2 SARS-CoV-2 repurposing malaria mefloquine |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2021.651403/full |
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