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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Published in:Frontiers in microbiology 2021-04, Vol.12, p.651403-651403
Main Authors: Shionoya, Kaho, Yamasaki, Masako, Iwanami, Shoya, Ito, Yusuke, Fukushi, Shuetsu, Ohashi, Hirofumi, Saso, Wakana, Tanaka, Tomohiro, Aoki, Shin, Kuramochi, Kouji, Iwami, Shingo, Takahashi, Yoshimasa, Suzuki, Tadaki, Muramatsu, Masamichi, Takeda, Makoto, Wakita, Takaji, Watashi, Koichi
Format: Article
Language:English
Subjects:
COVID-19
malaria
mefloquine
Microbiology
repurposing
SARS-CoV-2
severe acute respiratory syndrome-related coronavirus 2
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Summary: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 = 1.28 μM, IC = 2.31 μM, and IC = 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.
ISSN:1664-302X
1664-302X
DOI:10.3389/fmicb.2021.651403