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

• DOI: 10.3389/fmicb.2021.651403
• Publication Date: 2021-04-30T04:39:29Z
• Authors: 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
• Keywords: Hydroxychloroquine; Coronavirus

Coronavirus disease 2019 (COVID-19) has caused serious public health, social, and economic damage worldwide effective drugs that prevent or cure COVID-19 are urgently needed. Approved including Hydroxychloroquine, Remdesivir Interferon were reported to inhibit the infection propagation of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), however, their clinical efficacies have not yet been well demonstrated. To identify with higher antiviral potency, we screened approved anti-parasitic/anti-protozoal identified an anti-malarial drug, Mefloquine, which showed highest anti-SARS-CoV-2 activity among tested compounds. Mefloquine than Hydroxychloroquine in VeroE6/TMPRSS2 Calu-3 cells, IC 50 = 1.28 μM, 90 2.31 99 4.39 μM cells. inhibited viral entry after attachment target cell. Combined treatment Nelfinavir, a replication inhibitor, synergistic activity. Our mathematical modeling based on drug concentration lung predicted administration at standard dosage could decline dynamics patients, reduce cumulative load 7% shorten time until virus elimination by 6.1 days. These data cumulatively underscore as inhibitor.