Abstract：
UNASSIGNED: Vector-borne infectious diseases contribute significantly to global mortality, with over 700,000 annual deaths, and malaria alone accounts for more than 400,000 of these fatalities. Anopheles gambiae, a prominent mosquito species, serves as a primary vector for transmitting malaria to humans. To address this issue, researchers have identified the D1-like dopamine receptor (DAR), specifically DOP2, as a promising target for developing new insecticides.
METHODS: The three-dimensional structure of DOP2 from A. gambiae was unavailable; in-silico approach was used to model and validate DOP2 structure. The Discovery Studio 2021 program was used to identify potential binding sites on DOP2. Virtual screening of 235 anti-parasitic compounds was performed against DOP2 using PyRx 0.8.
RESULTS: The screening demonstrated strong binding and interactions with active site residues of DOP2 for five compounds: Diclazuril, Kaempferol, Deracoxib, Clindamycin, and Diaveridine. These compounds exhibited higher binding affinity values compared to the control (Asenapine). In addition, the predicted physiochemical properties for these compounds were within acceptable ranges and there were no violations in drug-likeness properties.
UNASSIGNED: These compounds show promise as potential new insecticides targeting A. gambiae mosquito by inhibiting the DOP2 protein. However, additional experimental validation is required to optimize their efficacy as DOP2 inhibitors.
METHODS: The three-dimensional structure of DOP2 from A. gambiae was unavailable; in-silico approach was used to model and validate DOP2 structure. The Discovery Studio 2021 program was used to identify potential binding sites on DOP2. Virtual screening of 235 anti-parasitic compounds was performed against DOP2 using PyRx 0.8.
RESULTS: The screening demonstrated strong binding and interactions with active site residues of DOP2 for five compounds: Diclazuril, Kaempferol, Deracoxib, Clindamycin, and Diaveridine. These compounds exhibited higher binding affinity values compared to the control (Asenapine). In addition, the predicted physiochemical properties for these compounds were within acceptable ranges and there were no violations in drug-likeness properties.
UNASSIGNED: These compounds show promise as potential new insecticides targeting A. gambiae mosquito by inhibiting the DOP2 protein. However, additional experimental validation is required to optimize their efficacy as DOP2 inhibitors.
摘要：
■病媒传染病对全球死亡率的贡献很大，每年有超过70万人死亡，仅疟疾就造成了40多万人的死亡。冈比亚按蚊,一种突出的蚊子，作为将疟疾传播给人类的主要媒介。为了解决这个问题，研究人员已经确定了D1样多巴胺受体（DAR），特别是DOP2，作为开发新杀虫剂的有希望的目标。
方法：无法获得冈比亚DOP2的三维结构；计算机模拟方法用于建模和验证DOP2结构。DiscoveryStudio2021计划用于鉴定DOP2上的潜在结合位点。使用PyRx0.8针对DOP2进行235种抗寄生虫化合物的虚拟筛选。
结果：筛选证明了五种化合物与DOP2的活性位点残基的强结合和相互作用：山奈酚,德拉考昔,克林霉素,还有Diaveridine.与对照(Asenapine)相比,这些化合物表现出更高的结合亲和力值。此外,这些化合物的预测生理化学性质在可接受的范围内，并且没有违反药物相似特性。
■这些化合物有望通过抑制DOP2蛋白而成为针对冈比亚蚊子的潜在新型杀虫剂。然而,需要额外的实验验证来优化其作为DOP2抑制剂的功效.
方法：无法获得冈比亚DOP2的三维结构；计算机模拟方法用于建模和验证DOP2结构。DiscoveryStudio2021计划用于鉴定DOP2上的潜在结合位点。使用PyRx0.8针对DOP2进行235种抗寄生虫化合物的虚拟筛选。
结果：筛选证明了五种化合物与DOP2的活性位点残基的强结合和相互作用：山奈酚,德拉考昔,克林霉素,还有Diaveridine.与对照(Asenapine)相比,这些化合物表现出更高的结合亲和力值。此外,这些化合物的预测生理化学性质在可接受的范围内，并且没有违反药物相似特性。
■这些化合物有望通过抑制DOP2蛋白而成为针对冈比亚蚊子的潜在新型杀虫剂。然而,需要额外的实验验证来优化其作为DOP2抑制剂的功效.
