{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:06:05Z","timestamp":1785434765447,"version":"3.56.0"},"reference-count":54,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["W81XWH2010386"],"award-info":[{"award-number":["W81XWH2010386"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["75N93022C00036"],"award-info":[{"award-number":["75N93022C00036"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["75N93022C00036"],"award-info":[{"award-number":["75N93022C00036"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["S10OD030394"],"award-info":[{"award-number":["S10OD030394"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Malaria remains a global health threat exacerbated by emerging resistance to antimalarial therapies and insecticides, climate-driven outbreaks, and limited chemoprotective options. Here, we report the characterization of\n                    <jats:bold>RUPB-61<\/jats:bold>\n                    , the first orally bioavailable inhibitor of Plasmodium falciparum cGMP-dependent protein kinase (PfPKG).\n                    <jats:bold>RUPB-61<\/jats:bold>\n                    prevents infection by\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    and\n                    <jats:italic>P. cynomolgi<\/jats:italic>\n                    sporozoites, including the formation of hypnozoites by the latter. A single oral dose blocks liver infection by P. berghei sporozoites\n                    <jats:italic>in vivo<\/jats:italic>\n                    , demonstrating efficacy consistent with further development as a once-weekly prophylaxis based on pharmacokinetic modeling. The compound retains activity against field isolates resistant to chloroquine, mefloquine, cycloguanil, sulfadoxine and pyrimethamine, suggesting low likelihood of cross-resistance to existing antimalarials. Structural studies and free energy-based modeling guided-compound design prospectively validated the predictive accuracy of an\n                    <jats:italic>in silico<\/jats:italic>\n                    model of PfPKG interactions with this chemotype. While selectivity profiling identified off-target activity against human kinases, structural modeling provides a clear path for optimization. These results establish PfPKG inhibitors as promising candidates for chemoprevention and support further preclinical development of the\n                    <jats:bold>RUPB-61<\/jats:bold>\n                    chemotype.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1014322","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:38:41Z","timestamp":1785433121000},"page":"e1014322","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["An orally available PfPKG inhibitor blocks Plasmodium\u2019s infection of the liver"],"prefix":"10.1371","volume":"22","author":[{"given":"Hanna","family":"Dhiyebi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aminata","family":"Mbaye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anusha","family":"Thaniana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Gilleran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler","family":"Eck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kutub","family":"Ashraf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Kudyba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve","family":"Seibold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin 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