{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T04:35:27Z","timestamp":1789792527737,"version":"4.0.1"},"reference-count":86,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"vor","delay-in-days":56,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biochemistry Research International"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Malaria remains a significant and worldwide health threat with increasing resistance to current treatments, stimulating the demand for innovative approaches in pursuing drug discovery. This systematic review integrates the progress made from 2014 through 2024 regarding molecular methods like gene expression profiling, molecular docking and machine learning to understand the biology of\n                      <jats:italic>Plasmodium<\/jats:italic>\n                      and identify new drug targets and compounds, focusing on herbal remedies and computational methods.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methodology<\/jats:title>\n                    <jats:p>Several studies were found using a PRISMA\u2010guided search of PubMed, Scopus and Web of Science (64 studies found). The data extracted were gene expression outcomes, docking affinities, ML models and experimental validations (in vitro\/in vivo).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Molecular docking emerged as the dominant technique (32.37%), followed by in vitro antiplasmodial assays (14.39%), ADMET profiling (10.79%) and gene expression studies (3.60%). RNA\u2010seq analysis revealed key host and parasite genes modulated by herbal treatments, including those involved in apoptosis and inflammation. Notably, compounds like isorhamnetin and myricetin 3\u2010O\u2010glucoside showed exceptionally high binding affinities to\n                      <jats:italic>Plasmepsin II<\/jats:italic>\n                      and\n                      <jats:italic>Plasmodium falciparum<\/jats:italic>\n                      lactate dehydrogenase (PfLDH) (\u0394G\u2009&lt;\u2009\u221213\u2009kcal\/mol). ML models like random forest and support vector machine (SVM) exhibited high predictive results (AUC value up to 0.87) for bioactivity and resistance patterns that showed flavonoids (quercetin) and terpenoids (eugenol) as good candidates. Pathways that are often attacked are haemoglobin degradation, glycolysis, pyrimidine metabolism and protein synthesis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Multiomics, docking and ML integration improve the target identification and prioritise the compounds. This review illustrates the great potential of molecular techniques for the development of drugs against antimalarial helicases that are not resistant to drug therapy. However, in vivo data holes and methodology inconsistency limit clinical translation. Future work should include standardisation of protocols and studies of synergistic combinations of phytochemicals.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/bri\/2724332","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T18:17:51Z","timestamp":1772993871000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Gene Expression, Docking and Machine Learning in Malaria Drug Discovery: A Systematic Review"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1077-3782","authenticated-orcid":false,"given":"Reuben Samson","family":"Dangana","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0672-5155","authenticated-orcid":false,"given":"Israel Ehizuelen","family":"Ebhohimen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8827-8191","authenticated-orcid":false,"given":"Samson Anjikwi","family":"Malgwi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1856-5697","authenticated-orcid":false,"given":"Samuel Chima","family":"Ugbaja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8337-6294","authenticated-orcid":false,"given":"Moses","family":"Okpeku","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,26]]},"reference":[{"key":"e_1_2_13_1_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-022-04340-1"},{"key":"e_1_2_13_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-72427-7"},{"key":"e_1_2_13_3_2","unstructured":"ShinH.-I. 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