Identification of inositol monophosphatase as a broad-spectrum antiviral target of ivermectin
Issued Date
2024-03-01
Resource Type
eISSN
10969071
Scopus ID
2-s2.0-85188494033
Pubmed ID
38511598
Journal Title
Journal of medical virology
Volume
96
Issue
3
Rights Holder(s)
SCOPUS
Bibliographic Citation
Journal of medical virology Vol.96 No.3 (2024) , e29552
Suggested Citation
Jitobaom K., Peerapen P., Boonyuen U., Meewan I., Boonarkart C., Sirihongthong T., Thongon S., Thongboonkerd V., Auewarakul P. Identification of inositol monophosphatase as a broad-spectrum antiviral target of ivermectin. Journal of medical virology Vol.96 No.3 (2024) , e29552. doi:10.1002/jmv.29552 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/97791
Title
Identification of inositol monophosphatase as a broad-spectrum antiviral target of ivermectin
Corresponding Author(s)
Other Contributor(s)
Abstract
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.