2023年3月9日
Potential anti-mpox virus activity of atovaquone, mefloquine, and molnupiravir, and their potential use as treatments.
The Journal of infectious diseases
- 巻
- 228
- 号
- 5
- 開始ページ
- 591
- 終了ページ
- 603
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1093/infdis/jiad058
- 出版者・発行元
- Oxford University Press ({OUP})
BACKGROUND: Mpox virus (MPXV) is a zoonotic orthopoxvirus and caused an outbreak in 2022. Although tecovirimat and brincidofovir are approved as anti-smallpox drugs, their effects in mpox patients have not been well documented. In this study, by a drug repurposing approach, we identified potential drug candidates for treating mpox and predicted their clinical impacts by mathematical modeling. METHODS: We screened approved 132 drugs using an MPXV infection cell system. We quantified antiviral activities of hit drugs by measuring intracellular viral DNA and analyzed the modes of action by time-of-addition assay and electron microscopic analysis. We further predicted the efficacy of drugs under clinical concentrations by mathematical simulation and examined combination treatment. RESULTS: Atovaquone, mefloquine, and molnupiravir exhibited anti-MPXV activity, with 50% inhibitory concentrations of 0.51-5.2 μM, which was more potent than cidofovir. Whereas mefloquine was suggested to inhibit viral entry, atovaquone and molnupiravir targeted post-entry process. Atovaquone was suggested to exert its activity through inhibiting dihydroorotate dehydrogenase. Combining atovaquone with tecovirimat enhanced the anti-MPXV effect of tecovirimat. Quantitative mathematical simulations predicted that atovaquone can promote viral clearance in patients by seven days at clinically relevant drug concentrations. CONCLUSION: These data suggest that atovaquone would be potential candidates for treating mpox.
- リンク情報
- ID情報
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- DOI : 10.1093/infdis/jiad058
- ISSN : 0022-1899
- ISSN : 1537-6613
- ORCIDのPut Code : 136057501
- PubMed ID : 36892247
- PubMed Central 記事ID : PMC10469127