{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T17:53:39Z","timestamp":1785779619954,"version":"3.56.0"},"reference-count":64,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100008895","name":"Tertiary Education Trust Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008895","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Tropical Med Int Health"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The emergence of artemisinin resistance in Plasmodium falciparum threatens the sustainability of malaria control programs and underscores the need for new therapeutic strategies. Recently, two proteins, RAD5 (PfRAD5) and WD40\u2010repeat protein 11 (PfWD11), have been implicated in parasite survival and drug resistance. Their druggability, however, remains underexplored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We integrated computational and experimental approaches to assess PfRAD5 and PfWD11 as antimalarial targets. Structural models were retrieved from AlphaFold and aligned with orthologues across Plasmodium species. A library of 216 antibiotics was screened by molecular docking, and molecular dynamics simulations. Top\u2010ranked compounds were tested against P. falciparum 3D7 cultures in\u00a0vitro, alone and in combination, and gene expression changes in PfRAD5 and PfWD11 were quantified by qPCR. Docking identified strong binders to PfRAD5 (talampicillin, dicloxacillin, raltegravir) and PfWD11 (cervinomycin A2 monoacetate, eAmSPC 2593, puromycin).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Molecular dynamics confirmed the stability of protein\u2013ligand complexes. In\u00a0vitro, puromycin exhibited the highest inhibition (85% at 100 \u03bcg\/mL), while combinations enhanced activity. The triple combination (puromycin + raltegravir + dicloxacillin) achieved complete inhibition, and puromycin + chloroquine exhibited synergistic effects at in a concentration\u2010dependent manner. qPCR showed consistent downregulation of PfRAD5 and PfWD11 following puromycin\u2010based treatments, whereas chloroquine alone upregulated PfRAD5 expression. PfRAD5 and PfWD11 represent novel antimalarial targets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Repurposed antibiotics, particularly puromycin in synergistic regimens, offer a cost\u2010effective strategy to counteract emerging resistance and accelerate therapeutic development.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/tmi.70147","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T12:03:56Z","timestamp":1777896236000},"page":"1093-1114","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Repositioning Antibiotics Against\n                    <i>Plasmodium falciparum<\/i>\n                    RAD5 and\n                    <scp>WD11<\/scp>\n                    as Novel Antimalarial Targets"],"prefix":"10.1111","volume":"31","author":[{"given":"Abdullah S.","family":"Albaqami","sequence":"first","affiliation":[{"name":"Department of Medical Laboratory Sciences College of Applied Medical Sciences, University of Bisha  Bisha Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9470-8488","authenticated-orcid":false,"given":"Oluwafemi Adebayo","family":"Oyewole","sequence":"additional","affiliation":[{"name":"Department of Microbiology School of Life Sciences, Federal University of Technology  Minna Niger State Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalid Mohamed","family":"Adam","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Sciences College of Applied Medical Sciences, University of Bisha  Bisha Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,4]]},"reference":[{"key":"e_1_2_10_2_1","volume-title":"World Malaria Report 2023","author":"WHO","year":"2023"},{"key":"e_1_2_10_3_1","first-page":"e26","article-title":"The Future of Antimalarial Therapy: Resistance, Treatment, and Elimination","volume":"24","author":"Rosenthal P. 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