{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:56:49Z","timestamp":1790780209765,"version":"4.1.0"},"reference-count":55,"publisher":"American Society for Microbiology","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2025-00517986"],"award-info":[{"award-number":["RS-2025-00517986"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Regional Innovation System & Education","award":["2025-RISE-10-002"],"award-info":[{"award-number":["2025-RISE-10-002"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      The discovery of novel anti-malarial drugs has become urgent due to increasing drug resistance. Our previous work identified ONX-0914, which targets parasite proteolytic systems, as promising against\n                      <jats:italic toggle=\"yes\">Plasmodium falciparum<\/jats:italic>\n                      . This study aims to further evaluate the antiplasmodial activity of ONX-0914 and related proteasome inhibitors (PIs) against various\n                      <jats:italic toggle=\"yes\">Plasmodium<\/jats:italic>\n                      strains. The\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      antimalarial activity of the inhibitors was evaluated against the\n                      <jats:italic toggle=\"yes\">Plasmodium knowlesi<\/jats:italic>\n                      A1H1 strain and compared with that against the chloroquine (CQ)-sensitive\n                      <jats:italic toggle=\"yes\">P. falciparum<\/jats:italic>\n                      3D7 strain. Potent synergistic interactions between compounds and artemisinin (ART) were analyzed against PkA1H1 and ART-resistant PfDd2R539T(+) using an isobologram. To explore the mode of action, the disruption of the ubiquitin-proteasome system (UPS) in PkA1H1 and Pf3D7 was investigated.\n                      <jats:italic toggle=\"yes\">In vivo<\/jats:italic>\n                      efficacy of ONX-0914 was further validated against CQ-resistant\n                      <jats:italic toggle=\"yes\">Plasmodium yoelii<\/jats:italic>\n                      . PIs significantly inhibited PkA1H1 proliferation with low-nanomolar IC\n                      <jats:sub>50<\/jats:sub>\n                      values; ONX-0914 and LU-005i were more potent against PkA1H1 than Pf3D7, and effectively blocked multiple blood stages. Inhibition of parasite growth correlated with potent disruption of UPS at nanomolar concentrations (IC\n                      <jats:sub>50<\/jats:sub>\n                      &lt; 50 nM). ONX-0914 demonstrated strong synergistic activity with ART and other PIs (\u2211FIC50 &lt; 0.8).\n                      <jats:italic toggle=\"yes\">In vivo<\/jats:italic>\n                      , ONX-0914 significantly suppressed\n                      <jats:italic toggle=\"yes\">P. yoelii<\/jats:italic>\n                      infection, improving lifespan, with \u205384% efficacy at an intraperitoneal (IP) dose of 20 mg\/kg, and \u205390% in combination with artemisinin at a dose of 10 mg\/kg (IP). Further optimization of the structure and dosing regimen is able to enhance the therapeutic potential of PIs as potential antimalarial drug candidates.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00382-26","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:11:46Z","timestamp":1790777506000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Anti-plasmodial activity of proteasome inhibitors against various\n                    <i>Plasmodium<\/i>\n                    species: a preclinical evaluation"],"prefix":"10.1128","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-5615-5670","authenticated-orcid":true,"given":"Nguyen","family":"Van Truong","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01mh5ph17","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Tropical Medicine, Kangwon National 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