Identification of inositol monophosphatase as a broad-spectrum antiviral target of ivermectin
© 2024 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC..
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.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2024 |
---|---|
Erschienen: |
2024 |
Enthalten in: |
Zur Gesamtaufnahme - volume:96 |
---|---|
Enthalten in: |
Journal of medical virology - 96(2024), 3 vom: 20. März, Seite e29552 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Jitobaom, Kunlakanya [VerfasserIn] |
---|
Links: |
---|
Anmerkungen: |
Date Completed 22.03.2024 Date Revised 22.03.2024 published: Print Citation Status MEDLINE |
---|
doi: |
10.1002/jmv.29552 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM370011767 |
---|
LEADER | 01000caa a22002652 4500 | ||
---|---|---|---|
001 | NLM370011767 | ||
003 | DE-627 | ||
005 | 20240323001636.0 | ||
007 | cr uuu---uuuuu | ||
008 | 240322s2024 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1002/jmv.29552 |2 doi | |
028 | 5 | 2 | |a pubmed24n1341.xml |
035 | |a (DE-627)NLM370011767 | ||
035 | |a (NLM)38511598 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Jitobaom, Kunlakanya |e verfasserin |4 aut | |
245 | 1 | 0 | |a Identification of inositol monophosphatase as a broad-spectrum antiviral target of ivermectin |
264 | 1 | |c 2024 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 22.03.2024 | ||
500 | |a Date Revised 22.03.2024 | ||
500 | |a published: Print | ||
500 | |a Citation Status MEDLINE | ||
520 | |a © 2024 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC. | ||
520 | |a 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 | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a antiviral | |
650 | 4 | |a inositol monophosphatase | |
650 | 4 | |a ivermectin | |
650 | 4 | |a lithium chloride | |
650 | 4 | |a phosphatidylinositol‐4‐phosphate | |
650 | 4 | |a thermal proteomic profiling | |
650 | 7 | |a myo-inositol-1 (or 4)-monophosphatase |2 NLM | |
650 | 7 | |a EC 3.1.3.25 |2 NLM | |
650 | 7 | |a Ivermectin |2 NLM | |
650 | 7 | |a 70288-86-7 |2 NLM | |
650 | 7 | |a 5'-Nucleotidase |2 NLM | |
650 | 7 | |a EC 3.1.3.5 |2 NLM | |
650 | 7 | |a Inositol |2 NLM | |
650 | 7 | |a 4L6452S749 |2 NLM | |
650 | 7 | |a Antiviral Agents |2 NLM | |
650 | 7 | |a Phosphoric Monoester Hydrolases |2 NLM | |
650 | 7 | |a EC 3.1.3.2 |2 NLM | |
700 | 1 | |a Peerapen, Paleerath |e verfasserin |4 aut | |
700 | 1 | |a Boonyuen, Usa |e verfasserin |4 aut | |
700 | 1 | |a Meewan, Ittipat |e verfasserin |4 aut | |
700 | 1 | |a Boonarkart, Chompunuch |e verfasserin |4 aut | |
700 | 1 | |a Sirihongthong, Thanyaporn |e verfasserin |4 aut | |
700 | 1 | |a Thongon, Songkran |e verfasserin |4 aut | |
700 | 1 | |a Thongboonkerd, Visith |e verfasserin |4 aut | |
700 | 1 | |a Auewarakul, Prasert |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Journal of medical virology |d 1990 |g 96(2024), 3 vom: 20. März, Seite e29552 |w (DE-627)NLM000285676 |x 1096-9071 |7 nnns |
773 | 1 | 8 | |g volume:96 |g year:2024 |g number:3 |g day:20 |g month:03 |g pages:e29552 |
856 | 4 | 0 | |u http://dx.doi.org/10.1002/jmv.29552 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 96 |j 2024 |e 3 |b 20 |c 03 |h e29552 |