| 冉稳坐,曹洪玉,唐乾,王立皓,郑学仿.化学通报,2025,88(3):328-334. |
| 基于DC-SIGN筛选含葡萄糖基化合物抑制病毒反式感染 |
| Screening of glucose-containing compounds to inhibit virus trans-infection based on DC-SIGN |
| 投稿时间：2024-08-19 修订日期：2024-11-26 |
| DOI： |
| 中文关键词: 异榭皮苷 DC-SIGN 分子对接 分子动力学模拟 拉伸分子动力学模拟 |
| 英文关键词:Hirsutrin DC-SIGN Molecular docking Molecular dynamics Steered molecular dynamics |
| 基金项目:国家自然科学基金项目(21571025,21601024,21601025)、辽宁省教育厅基本科研项目(LJ212411258006)、大连大学学科建设专项(学科交叉项目)(DLUXK-2023-YB-007)和大连大学平台科研项目(202101ZD01)资助 |
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| 中文摘要: |
| DC-SIGN碳水化合物识别域与单糖结合产生生物活性，是抑制病毒反式感染细胞的潜在靶点。目前实验研究表明葡萄糖类化合物异榭皮苷，红景天苷，汉黄苓苷等可抑制SARS-CoV-2感染。本研究通过分子动力学模拟等方法理解含糖苷分子结合DC-SIGN碳水化合物识别域机理，确定抗病毒效果及机制。分子对接表明，红景天苷具有葡萄糖基结合DC-SIGN的经典构象。分子动力学模拟表明，异榭皮苷、红景天苷具有葡萄糖基结合DC-SIGN的相似构象，而汉黄苓苷、连翘苷与关键氨基酸形成氢键相互作用较少。异榭皮苷从DC-SIGN碳水化合物识别域拉伸到4 ?时拉力最大(1540.443 pN)，红景天苷在3.9 ?时拉力最大(1640.999 pN)，显示其更难分离。综上表明，异榭皮苷、红景天苷可能与DC-SIGN碳水化合物识别域结合，可能作为治疗这些病毒感染的候选药物。 |
| 英文摘要: |
| The DC-SIGN carbohydrate recognition domain can bind to monosaccharides to generate biological activity, which is a potential target for inhibiting viral trans infection of cells. At present, experimental studies have shown that glucose compounds such as hirsutrin, salidroside and oroxindin can inhibit SARS-CoV-2 infection. This study aimed to understand the mechanism of glycosidic molecules binding to the DC-SIGN carbohydrate recognition domain through molecular dynamics simulations and other methods for understanding the antiviral effect and mechanism. Molecular docking results indicated that salidroside had a classical conformation of glucose based DC-SIGN binding. Molecular dynamics simulations have shown that hirsutrin and salidroside had similar conformations of glucose bound to DC-SIGN, while oroxindin and forsythin form fewer hydrogen bonding interactions with key amino acids. The maximum tensile strength (1540.443 pN) of hirsutrin was observed when stretched from the DC-SIGN carbohydrate recognition domain to 4 ?, while the maximum tensile strength (1640.999 pN) of salidroside was observed at 3.9 ?, indicating that it was more difficult to separate. All the data indicated that hirsutrin and salidroside could bind to the DC-SIGN carbohydrate recognition domain and could be candidate drugs for treating the viral infections. In conclusion, hirsutrin and salidroside may bind to the carbohydrate recognition domain of DC-SIGN, which could be candidate drugs for treating these viral infections. |
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