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目的:运用虚拟筛选技术从热毒宁注射液中筛选出抗鼻病毒3C蛋白酶的有效中药小分子抑制剂。方法:以热毒宁注射液中460种化合物为筛选目标,选取2个目前与鼻病毒治疗密切相关的靶点蛋白为受体,采用SYBYL分子对接的方法,以Total Score结合打分为标准筛选出得分最高的分子并观察其结合模式图,借助DiscoveryS tudio2016软件对其进行相互作用的分析,预测其结合模式及亲和力。结果:通过分子对接方法,筛选出5个符合条件(以打分函数Total-Score 6分以上为阈值,以Total-Score 9分以上为较好活性)且与靶点蛋白结合最好的中药小分子。其中,有2个小分子Total-Score打分最高,即与5FX5、5FX6蛋白活性位点的匹配度最高,并均超过其与自身配体结合打分,分别为似梨木双黄酮、绿原酸。结论:热毒宁注射液化学成分与鼻病毒3C蛋白酶相关靶点具有一定的结合和抑制效应。该结果可促进从传统中药中提取、设计以及实验合成新的抗鼻病毒药物。
OBJECTIVE: To screen out effective small molecule inhibitors of rhinovirus 3C protease from Rendunning injection by virtual screening technology. Methods: Forty-six compounds were selected as target. Two target proteins that are currently closely related to rhinovirus therapy were selected as the target. SYBYL molecular docking method was used to scoring the target protein by Total Score. Scored the highest molecular and observed its binding patterns, with the help of DiscoverySoft2016 software interaction analysis, prediction of its binding patterns and affinity. Results: By molecular docking method, we screened 5 small molecules of traditional Chinese medicine (with the Total-Score of 6 or more as the threshold and more than 9 points of Total-Score as the best activity) . Among them, there are two small molecules Total-Score scoring the highest, that 5FX5, 5FX6 active site of the highest match, and more than its own ligand combination score, respectively, like pear wood flavonoids, chlorogenic acid. CONCLUSION: The chemical constituents of Reverining injection have a certain binding and inhibitory effect on the target of rhinovirus 3C protease. This result can facilitate the extraction, design and experimental synthesis of new anti-rhinovirus drugs from traditional Chinese medicines.