Identification of inositol monophosphatase as a broad‐spectrum antiviral target of ivermectin
Kunlakanya Jitobaom, Paleerath Peerapen, Usa Boonyuen, Ittipat Meewan, Chompunuch Boonarkart, Thanyaporn Sirihongthong, Songkran Thongon, Visith Thongboonkerd, Prasert Auewarakul
Journal of Medical Virology, doi:10.1002/jmv.29552
Ivermectin has broad-spectrum antiviral activities. Despite the failure in clinical application of COVID-19, it can serve as a lead compound for the development of more effective broad-spectrum antivirals, for which a better understanding of its antiviral mechanisms is essential. We thus searched for potential novel targets of ivermectin in host cells by label-free thermal proteomic profiling using Huh-7 cells. Inositol monophosphatase (IMPase) was found among the proteins with shifted thermal stability by ivermectin. Ivermectin could inhibit IMPase activity and reduce cellular myo-inositol and phosphatidylinositol-4-phosphate levels. On the other hand, inositol could impair the antiviral activity of ivermectin and lithium, an IMPase inhibitor with known antiviral activity. As phosphatidylinositol phosphate is crucial for the replication of many RNA viruses, inhibition of cellular myo-inositol biosynthesis may be an important antiviral mechanism of ivermectin. Hence, inhibition of IMPase could serve as a potential target for broad-spectrum antiviral development.
AUTHOR CONTRIBUTIONS Kunlakanya
CONFLICT OF INTEREST STATEMENT The authors declare no conflict of interest.
SUPPORTING INFORMATION Additional supporting information can be found online in the Supporting Information section at the end of this article. How to cite this article: Jitobaom K, Peerapen P, Boonyuen
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