{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T23:06:31Z","timestamp":1791932791449,"version":"4.3.4"},"reference-count":59,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,4,2]],"date-time":"2022-04-02T00:00:00Z","timestamp":1648857600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The global burden of malaria and toxoplasmosis has been limited by the use of efficacious anti-parasitic agents, however, emerging resistance in Plasmodium species and Toxoplasma gondii threatens disease control worldwide, implying that new agents\/therapeutic targets are urgently needed. Nuclear localization signal (NLS)-dependent transport into the nucleus, mediated by members of the importin (IMP) superfamily of nuclear transporters, has shown potential as a target for intervention to limit viral infection. Here, we show for the first time that IMP\u03b1 from P. falciparum and T. gondii have promise as targets for small molecule inhibitors. We use high-throughput screening to identify agents able to inhibit P. falciparum IMP\u03b1 binding to a P. falciparum NLS, identifying a number of compounds that inhibit binding in the \u00b5M-nM range, through direct binding to P. falciparum IMP\u03b1, as shown in thermostability assays. Of these, BAY 11-7085 is shown to be a specific inhibitor of P. falciparum IMP\u03b1-NLS recognition. Importantly, a number of the inhibitors limited growth by both P. falciparum and T. gondii. The results strengthen the hypothesis that apicomplexan IMP\u03b1 proteins have potential as therapeutic targets to aid in identifying novel agents for two important, yet neglected, parasitic diseases.<\/jats:p>","DOI":"10.3390\/cells11071201","type":"journal-article","created":{"date-parts":[[2022,4,3]],"date-time":"2022-04-03T02:59:52Z","timestamp":1648954792000},"page":"1201","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["High-Throughput Screening to Identify Inhibitors of Plasmodium falciparum Importin \u03b1"],"prefix":"10.3390","volume":"11","author":[{"given":"Sujata B.","family":"Walunj","sequence":"first","affiliation":[{"name":"Nuclear Signaling Laboratory, Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia"},{"name":"Molecular Parasitology Laboratory, Department of Biosciences and Bioengineering, IIT Bombay, Powai, Mumbai 400076, India"},{"name":"IITB-Monash Research Academy, IIT Bombay, Mumbai 400076, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manisha M.","family":"Dias","sequence":"additional","affiliation":[{"name":"Nuclear Signaling Laboratory, Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3485-8414","authenticated-orcid":false,"given":"Chhaminder","family":"Kaur","sequence":"additional","affiliation":[{"name":"Molecular Parasitology Laboratory, Department of Biosciences and Bioengineering, IIT Bombay, Powai, Mumbai 400076, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kylie M.","family":"Wagstaff","sequence":"additional","affiliation":[{"name":"Nuclear Signaling Laboratory, Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishakha","family":"Dey","sequence":"additional","affiliation":[{"name":"Molecular Parasitology Laboratory, Department of Biosciences and Bioengineering, IIT Bombay, Powai, Mumbai 400076, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Hick","sequence":"additional","affiliation":[{"name":"Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swati","family":"Patankar","sequence":"additional","affiliation":[{"name":"Molecular Parasitology Laboratory, Department of Biosciences and Bioengineering, IIT Bombay, Powai, Mumbai 400076, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5115-4745","authenticated-orcid":false,"given":"David A.","family":"Jans","sequence":"additional","affiliation":[{"name":"Nuclear Signaling Laboratory, Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/j.cell.2016.07.055","article-title":"Malaria: Biology and Disease","volume":"167","author":"Cowman","year":"2016","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"281","DOI":"10.4103\/0974-777X.83536","article-title":"Toxoplasmosis: A global threat","volume":"3","author":"Furtado","year":"2011","journal-title":"J. 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