{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T01:35:33Z","timestamp":1783215333603,"version":"3.54.6"},"reference-count":37,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T00:00:00Z","timestamp":1749168000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deanship of Graduate Studies and Scientific Research at the University of Bisha","award":["UB-GRP-39-1444"],"award-info":[{"award-number":["UB-GRP-39-1444"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Acute Myeloid Leukemia (LAML) is a life-threatening hematological malignancy, and the DEAD-box helicase 3 X-linked (DDX3X) gene is a potential yet underexplored target gene for LAML. Biomolecules derived from medicinal plants like Aerva javanica offer a great source of therapeutic candidates. This study aimed to investigate the role of DDX3X in LAML and identify plant-derived biomolecules that could inhibit DDX3X using computational approaches. Pan-cancer mutational profiling, a transcriptomic analysis, survival, protein\u2013protein interaction networks, and a principal component analysis (PCA) were employed to elucidate functional associations and transcriptomic divergence. Subsequently, biomolecules from A. javanica were subjected to in silico screening using molecular docking and ADMET profiling. The docking protocol was validated using RK-33, a known DDX3X inhibitor. DDX3X was found to be linked to key leukemogenic pathways, including Wnt\/\u03b2-catenin and MAPK signaling, indicating it to be a potential target. Molecular docking of A. javanica compounds revealed CIDs 15559724, 5490003, and 74819331 as potent DDX3X inhibitors with strong binding affinity and favorable pharmacokinetic and toxicity profiles compared to RK-33. This study highlights the importance of DDX3X in LAML pathogenesis and suggests targeting it using plant-derived inhibitors, which may require further in vitro and in vivo validation.<\/jats:p>","DOI":"10.3390\/ijms26125445","type":"journal-article","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T09:02:03Z","timestamp":1749200523000},"page":"5445","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Repurposing Biomolecules from Aerva javanica Against DDX3X in LAML: A Computer-Aided Therapeutic Approach"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6304-2943","authenticated-orcid":false,"given":"Abdulaziz","family":"Asiri","sequence":"first","affiliation":[{"name":"Department of Medical Laboratory Sciences, College of Applied Medical Sciences, University of Bisha, 255, Al Nakhil, Bisha 67714, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3509-7565","authenticated-orcid":false,"given":"Abdulwahed","family":"Alrehaily","sequence":"additional","affiliation":[{"name":"Biology Department, Faculty of Science, Islamic University of Madinah, Madinah 42351, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4189-4800","authenticated-orcid":false,"given":"Amer","family":"Al Ali","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Sciences, College of Applied Medical Sciences, University of Bisha, 255, Al Nakhil, Bisha 67714, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0125-4041","authenticated-orcid":false,"given":"Mohammed H.","family":"Abu-Alghayth","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Sciences, College of Applied Medical Sciences, University of Bisha, 255, Al Nakhil, Bisha 67714, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Munazzah","family":"Tasleem","sequence":"additional","affiliation":[{"name":"Department of Public Health, College of Applied Medical Sciences in Al-Namas, University of Bisha, Al-Namas City 67714, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16010","DOI":"10.1038\/nrdp.2016.10","article-title":"Acute myeloid leukaemia","volume":"2","author":"Khwaja","year":"2016","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Huang, P., and Zhang, J. (2025). Global leukemia burden and trends: A comprehensive analysis of temporal and spatial variations from 1990\u20132021 using GBD (Global Burden of Disease) data. BMC Public Health, 25.","DOI":"10.1186\/s12889-025-21428-w"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1007\/s00277-022-04843-6","article-title":"Mapping incidence and mortality of leukemia and its subtypes in 21 world regions in last three decades and projections to 2030","volume":"101","author":"Sharma","year":"2022","journal-title":"Ann. Hematol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Bawazir, A., Al-Zamel, N., Amen, A., Akiel, M.A., Alhawiti, N.M., and Alshehri, A. (2019). The burden of leukemia in the Kingdom of Saudi Arabia: 15 years period (1999\u20132013). BMC Cancer, 19.","DOI":"10.1186\/s12885-019-5897-5"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Zhou, Y., Huang, G., Cai, X., Liu, Y., Qian, B., and Li, D. (2024). Global, regional, and national burden of acute myeloid leukemia, 1990\u20132021: A systematic analysis for the global burden of disease study 2021. Biomark. Res., 12.","DOI":"10.1186\/s40364-024-00649-y"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.15537\/smj.2019.11.24584","article-title":"Overall survival of adult acute myeloid leukemia based on cytogenetic and molecular abnormalities during 5 years in a single center study","volume":"40","author":"Alsobhi","year":"2019","journal-title":"Saudi Med. J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1182\/asheducation-2016.1.348","article-title":"Mutations in AML: Prognostic and therapeutic implications","volume":"2016","author":"DiNardo","year":"2016","journal-title":"Hematol. Am. Soc. Hematol. Educ. Program"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s12943-021-01325-7","article-title":"DDX3X: Structure, physiologic functions and cancer","volume":"20","author":"Mo","year":"2021","journal-title":"Mol. Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"198352","DOI":"10.1016\/j.virusres.2021.198352","article-title":"DEAD-box RNA helicases: The driving forces behind RNA metabolism at the crossroad of viral replication and antiviral innate immunity","volume":"296","author":"Ali","year":"2021","journal-title":"Virus Res."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Ryan, C.S., and Schr\u00f6der, M. (2022). The human DEAD-box helicase DDX3X as a regulator of mRNA translation. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.1033684"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"He, Y.-N., Han, X.R., Wang, D., Hou, J.L., and Hou, X.M. (2024). Dual mode of DDX3X as an atp-dependent RNA helicase and atp-independent nucleic acid chaperone. Biochem. Biophys. Res. Commun., 714.","DOI":"10.1016\/j.bbrc.2024.149964"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2412","DOI":"10.1074\/jbc.M115.700625","article-title":"Autoinhibitory interdomain interactions and subfamily-specific extensions redefine the catalytic core of the human DEAD-box protein DDX3","volume":"291","author":"Floor","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1261\/rna.079837.123","article-title":"A novel reporter for helicase activity in translation uncovers DDX3X interactions","volume":"30","author":"Wilkins","year":"2024","journal-title":"RNA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1016\/j.molmed.2023.06.003","article-title":"The variant landscape and function of DDX3X in cancer and neurodevelopmental disorders","volume":"29","author":"Gadek","year":"2023","journal-title":"Trends Mol. Med."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Lin, T.C. (2019). DDX3X Multifunctionally Modulates Tumor Progression and Serves as a Prognostic Indicator to Predict Cancer Outcomes. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21010281"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1007\/s11427-019-1605-0","article-title":"Splicing dysregulation in cancer: From mechanistic understanding to a new class of therapeutic targets","volume":"63","author":"Wang","year":"2020","journal-title":"Sci. Chin. Life Sci."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Vesuna, F., Akhrymuk, I., Smith, A., Winnard, P.T., Lin, S.C., Panny, L., Scharpf, R., Kehn-Hall, K., and Raman, V. (2022). RK-33, a small molecule inhibitor of host RNA helicase DDX3, suppresses multiple variants of SARS-CoV-2. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.959577"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1007\/s13237-022-00405-3","article-title":"Plant-derived natural products for drug discovery: Current approaches and prospects","volume":"65","author":"Nasim","year":"2022","journal-title":"Nucleus"},{"key":"ref_19","first-page":"268","article-title":"A review on the Pashanbheda plant Aerva javanica","volume":"25","author":"Movaliya","year":"2014","journal-title":"Int. J. Pharm. Sci. Rev. Res."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Thotathil, V., Sidiq, N., Fakhroo, A., and Sreerama, L. (2023). Phytochemical Analysis of Anastatica hierochuntica and Aerva javanica Grown in Qatar: Their Biological Activities and Identification of Some Active Ingredients. Molecules, 28.","DOI":"10.3390\/molecules28083364"},{"key":"ref_21","first-page":"453","article-title":"The NCI Genomic Data Commons as an engine for precision medicine","volume":"130","author":"Jensen","year":"2017","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"W98","DOI":"10.1093\/nar\/gkx247","article-title":"GEPIA: A web server for cancer and normal gene expression profiling and interactive analyses","volume":"45","author":"Tang","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.neo.2022.01.001","article-title":"UALCAN: An update to the integrated cancer data analysis platform","volume":"25","author":"Chandrashekar","year":"2022","journal-title":"Neoplasia"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Zhang, H., Cui, B., Zhou, Y., Wang, X., Wu, W., Wang, Z., Dai, Z., Cheng, Q., and Yang, K. (2021). B2M overexpression correlates with malignancy and immune signatures in human gliomas. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-84465-6"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1200\/PO.18.00321","article-title":"Majority of B2M-mutant and-deficient colorectal carcinomas achieve clinical benefit from immune checkpoint inhibitor therapy and are microsatellite instability-high","volume":"3","author":"Middha","year":"2019","journal-title":"JCO Precis. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"W556","DOI":"10.1093\/nar\/gkz430","article-title":"GEPIA2: An enhanced web server for large-scale expression profiling and interactive analysis","volume":"47","author":"Tang","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1097\/PPO.0b013e3181bdc2e0","article-title":"Overall survival: Still the gold standard: Why overall survival remains the definitive end point in cancer clinical trials","volume":"15","author":"Driscoll","year":"2009","journal-title":"Cancer J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2490","DOI":"10.1158\/1538-7445.AM2019-2490","article-title":"R2: Genomics analysis and visualization platform","volume":"79","author":"Koster","year":"2019","journal-title":"Cancer Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"D607","DOI":"10.1093\/nar\/gky1131","article-title":"STRING v11: Protein\u2013protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets","volume":"47","author":"Szklarczyk","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"W5","DOI":"10.1093\/nar\/gkab255","article-title":"ADMETlab 2.0: An integrated online platform for accurate and comprehensive predictions of ADMET properties","volume":"49","author":"Xiong","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.jmb.2007.06.050","article-title":"Crystal structure of conserved domains 1 and 2 of the human DEAD-box helicase DDX3X in complex with the mononucleotide AMP","volume":"372","author":"Collins","year":"2007","journal-title":"J. Mol. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Hsu, K.-C., Chen, Y.F., Lin, S.R., and Yang, J.M. (2011). iGEMDOCK: A graphical environment of enhancing GEMDOCK using pharmacological interactions and post-screening analysis. BMC Bioinform., 12.","DOI":"10.1186\/1471-2105-12-S1-S33"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Yang, S.N., Atkinson, S.C., Audsley, M.D., Heaton, S.M., Jans, D.A., and Borg, N.A. (2020). RK-33 is a broad-spectrum antiviral agent that targets DEAD-box RNA helicase DDX3X. Cells, 9.","DOI":"10.3390\/cells9010170"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"648","DOI":"10.15252\/emmm.201404368","article-title":"Targeting DDX 3 with a small molecule inhibitor for lung cancer therapy","volume":"7","author":"Bol","year":"2015","journal-title":"EMBO Mol. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3573","DOI":"10.1016\/j.celrep.2019.05.069","article-title":"The X-linked DDX3X RNA helicase dictates translation reprogramming and metastasis in melanoma","volume":"27","author":"Phung","year":"2019","journal-title":"Cell Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/S0022-2860(02)00406-4","article-title":"Methoxy group as an acceptor of proton in hydrogen bonds","volume":"642","author":"Palusiak","year":"2002","journal-title":"J. Mol. Struct."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.comptc.2015.06.013","article-title":"The effect of methoxy group rotation and hydrogen bonding on the redox properties of ubiquinone","volume":"1069","year":"2015","journal-title":"Comput. Theor. Chem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/12\/5445\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:47:40Z","timestamp":1760032060000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/12\/5445"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,6]]},"references-count":37,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["ijms26125445"],"URL":"https:\/\/doi.org\/10.3390\/ijms26125445","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,6]]}}}