Mefloquine, a Potent Anti-severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2) Drug as an Entry Inhibitor in vitro

被引:31
作者
Shionoya, Kaho [1 ,2 ]
Yamasaki, Masako [1 ,2 ]
Iwanami, Shoya [3 ,4 ]
Ito, Yusuke [4 ]
Fukushi, Shuetsu [5 ]
Ohashi, Hirofumi [1 ,2 ]
Saso, Wakana [1 ,6 ,7 ]
Tanaka, Tomohiro [8 ]
Aoki, Shin [9 ]
Kuramochi, Kouji [2 ]
Iwami, Shingo [3 ,4 ,10 ,11 ,12 ,13 ,14 ]
Takahashi, Yoshimasa [15 ,16 ]
Suzuki, Tadaki [17 ]
Muramatsu, Masamichi [1 ]
Takeda, Makoto [18 ]
Wakita, Takaji [1 ]
Watashi, Koichi [1 ,2 ,10 ,16 ,19 ]
机构
[1] Natl Inst Infect Dis, Dept Virol 2, Tokyo, Japan
[2] Tokyo Sci Univ, Dept Appl Biol Sci, Tokyo, Japan
[3] Nagoya Univ, Grad Sch Sci, Interdisciplinary Biol Lab iBLab, Div Biol Sci, Nagoya, Aichi, Japan
[4] Kyushu Univ, Dept Biol, Fac Sci, Fukuoka, Japan
[5] Natl Inst Infect Dis, Dept Virol 1, Tokyo, Japan
[6] Univ Tokyo, Inst Med Sci, Tokyo, Japan
[7] Natl Inst Infect Dis, AIDS Res Ctr, Tokyo, Japan
[8] Tokyo Univ Sci, Fac Pharmaceut Sci, Tokyo, Japan
[9] Tokyo Univ Sci, Res Inst Sci & Technol, Tokyo, Japan
[10] JST, MIRAI, Saitama, Japan
[11] Kyushu Univ, Inst Math Ind, Fukuoka, Japan
[12] Kyoto Univ, Inst Adv Study Human Biol ASHBi, Kyoto, Japan
[13] Japanese Fdn Canc Res JFCR, NEXT Ganken Program, Tokyo, Japan
[14] Sci Groove Inc, Fukuoka, Japan
[15] Natl Inst Infect Dis, Dept Immunol, Tokyo, Japan
[16] Natl Inst Infect Dis, Res Ctr Drug & Vaccine Dev, Tokyo, Japan
[17] Natl Inst Infect Dis, Dept Pathol, Tokyo, Japan
[18] Natl Inst Infect Dis, Dept Virol 3, Tokyo, Japan
[19] Kyoto Univ, Inst Frontier Life & Med Sci, Kyoto, Japan
基金
日本学术振兴会;
关键词
COVID-19; severe acute respiratory syndrome-related coronavirus 2; SARS-CoV-2; repurposing; malaria; mefloquine; coronavirus; HYDROXYCHLOROQUINE; CHLOROQUINE; SARS;
D O I
10.3389/fmicb.2021.651403
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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 mu M, IC90 = 2.31 mu M, and IC99 = 4.39 mu M 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.
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页数:12
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