DOAJ Open Access 2021

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

Kaho Shionoya Kaho Shionoya Masako Yamasaki Masako Yamasaki Shoya Iwanami +29 lainnya

Abstrak

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.

Topik & Kata Kunci

Microbiology

Penulis (34)

Kaho Shionoya

Masako Yamasaki

Shoya Iwanami

Yusuke Ito

Shuetsu Fukushi

Hirofumi Ohashi

Wakana Saso

Tomohiro Tanaka

Shin Aoki

Kouji Kuramochi

Shingo Iwami

Yoshimasa Takahashi

Tadaki Suzuki

Masamichi Muramatsu

Makoto Takeda

Takaji Wakita

Koichi Watashi

Format Sitasi

APA MLA BibTeX

Shionoya, K., Shionoya, K., Yamasaki, M., Yamasaki, M., Iwanami, S., Iwanami, S. et al. (2021). Mefloquine, a Potent Anti-severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2) Drug as an Entry Inhibitor in vitro. https://doi.org/10.3389/fmicb.2021.651403

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Informasi Jurnal

Tahun Terbit: 2021
Sumber Database: DOAJ
DOI: 10.3389/fmicb.2021.651403
Akses: Open Access ✓