| Autor: |
Daisuke Akazawa, Hirofumi Ohashi, Takayuki Hishiki, Takeshi Morita, Shoya Iwanami, Kwang Su Kim, Yong Dam Jeong, Eun-Sil Park, Michiyo Kataoka, Kaho Shionoya, Junki Mifune, Kana Tsuchimoto, Shinjiro Ojima, Aa Haeruman Azam, Shogo Nakajima, Hyeongki Park, Tomoki Yoshikawa, Masayuki Shimojima, Kotaro Kiga, Shingo Iwami, Ken Maeda, Tadaki Suzuki, Hideki Ebihara, Yoshimasa Takahashi, Koichi Watashi |
| Rok vydání: |
2022 |
| Popis: |
Monkeypox virus (MPXV) is a zoonotic orthopoxvirus that causes smallpox-like symptoms in humans and caused an outbreak in May 2022 that led the WHO to declare global health emergency. In this study, from a screening of approved-drug libraries using an MPXV infection cell system, atovaquone, mefloquine, and molnupiravir exhibited anti-MPXV activity, with 50% inhibitory concentrations of 0.51-5.2 μM, which is more potent than cidofovir. Whereas mefloquine was suggested to inhibit viral entry, atovaquone and molnupiravir targeted post-entry process to impair intracellular virion accumulation. Inhibitors of dihydroorotate dehydrogenase, an atovaquone’s target enzyme, showed conserved anti-MPXV activities. 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. Moreover, atovaquone and molnupiravir exhibited pan-Orthopoxvirus activity against vaccinia and cowpox viruses. These data suggest that atovaquone would be potential candidates for treating monkeypox. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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