Okafor Esther O, Bella-Omunagbe Mercy, Elugbadebo Temitope, Dokunmu Titilope M, Adebiyi Ezekiel
Covenant University Bioinformatics Research (CUBRe), Covenant University, Ota, Nigeria.
Department of Biochemistry, Covenant University, Ota, Ogun State, Nigeria.
BMC Infect Dis. 2025 Aug 19;25(1):1038. doi: 10.1186/s12879-025-11380-w.
Plasmodium falciparum subtilisin-like protease 2 (PfSUB2) is responsible for processing Plasmodium falciparum thrombospondin-related apical merozoite protein (PfTRAMP). These proteins are essential for asexual blood stage growth and RBC invasion and have, therefore, been identified as potential drug targets. This study predicted the three-dimensional structure of PfSUB2 and PfTRAMP and identified potential inhibitors using molecular docking methods. Five hundred nineteen compounds were docked against both proteins with AutoDock Vina in PyRx. Compounds 139,974,934 and 154,414,021 exhibited better binding affinities when compared to the standard inhibitors, PMSF, which highlights them as suitable inhibitors and potential antimalarials targeting PfTRAMP and PfSUB2. It also highlights 155,204,487 as a compound with dual antimalarial target potential, exhibiting a better binding affinity to PfTRAMP and PfSUB2. The study recommends 139,974,934, 154,414,021, and 155,204,487 as possible compounds for antimalarial drug development.
恶性疟原虫枯草杆菌蛋白酶样蛋白酶2（PfSUB2）负责处理恶性疟原虫血小板反应蛋白相关顶质体裂殖子蛋白（PfTRAMP）。这些蛋白质对于无性血液阶段的生长和红细胞入侵至关重要，因此已被确定为潜在的药物靶点。本研究预测了PfSUB2和PfTRAMP的三维结构，并使用分子对接方法鉴定了潜在的抑制剂。在PyRx中使用AutoDock Vina将519种化合物与这两种蛋白质进行对接。与标准抑制剂苯甲基磺酰氟（PMSF）相比，化合物139974934和154414021表现出更好的结合亲和力，这突出表明它们是合适的抑制剂以及靶向PfTRAMP和PfSUB2的潜在抗疟药物。它还突出表明155204487是一种具有双重抗疟靶点潜力的化合物，对PfTRAMP和PfSUB2表现出更好的结合亲和力。该研究推荐139974934、154414021和155204487作为抗疟药物开发的可能化合物。
