Identification of IMP Dehydrogenase as a Potential Target for Anti-Mpox Virus Agents
Takayuki Hishiki, Takeshi Morita, Daisuke Akazawa, Hirofumi Ohashi, Eun‐Sil Park, Michiyo Kataoka, Junki Mifune, Kaho Shionoya, Kana Tsuchimoto, Shinjiro Ojima, Aa Haeruman Azam, Shogo Nakajima, Madoka Kawahara, Tomoki Yoshikawa, Masayuki Shimojima, Kotaro Kiga, Ken Maeda, Tadaki Suzuki, Hideki Ebihara, Yoshimasa Takahashi, Koichi Watashi
Abstract
Mpox is a zoonotic disease caused by infection with the mpox virus, and a worldwide outbreak occurred in May 2022. The smallpox vaccine has recently been approved for clinical use against mpox in the United States. Although brincidofovir and tecovirimat are drugs approved for the treatment of smallpox by the U.S. Food and Drug Administration, their efficacy against mpox has not been established. Moreover, these drugs may present negative side effects. Therefore, new anti-mpox virus agents are needed. This study revealed that gemcitabine, trifluridine, and mycophenolic acid inhibited mpox virus propagation and exhibited broad-spectrum anti-orthopoxvirus activities. We also suggested IMP dehydrogenase as a potential target for the development of anti-mpox virus agents. By targeting this molecule, we identified a series of compounds with stronger anti-mpox virus activity than mycophenolic acid.