基于酚酸类结构研究抗流感病毒、 新冠病毒前体药物

	基于酚酸类结构研究抗流感病毒、新冠病毒前体药物
	侯博
导师	周俊
关键词	乙酰化酚酸环，流感病毒，新冠病毒，抑制剂 Acetylflicinic acid cycle, Flu virus, SARS-CoV-2, Inhibitors
摘要	季节性流感与新冠病毒的爆发在成人与小孩之间广泛传播，不仅感染率高而且造成全球成千上万人死亡。近年来出现的耐药株具有高变异性、高感染率、高致病性特点，加之现有药物耐药、供需不均、高价使得开发新的抗病毒药物极为迫切。化合物 zd-5 能简单、有效的大规模合成，具有双靶点抑制（ HA、 NA）效果，体外抗 A/B 型流感病毒活性在 0.52 uM-7.13 uM 之间，该化合物的有效性与安全性在动物实验中得到观察与证实。另一方面的工作是针对当前抗新冠病毒药物的稀缺性与有限性，应用基于靶点筛选方法，结合 LC/MS 导向分离手段从大羽鳞毛蕨（ Dryopteris wallichiana）中获得了在 Vero E6 细胞上有效果的化合物3，靶点研究揭示该类化合物主要作用于新冠病毒 3CLpro 蛋白。本研究提供了抗流感病毒活性化合物 zd-5 与抗新冠病毒活性分子 3，它们有助于新的抗病毒药物开发与利用。; Outbreaks of virus including the seasonal flu and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have spread throughout grown-ups and kids, within high infected rate and killing up to thousands of people in global annually. Highly variable, contagious, and pathogenic occasional drug-resistant strains emerged in recent years. In addition, existing drugs are resistant, overpriced and short supplies have highlighted the need to develop novel anti-virus therapeutics. Compound zd-5 can be synthesized simply and efficiently in large scale, having activities of NA and HA, and the anti-influenza activities of the Flu A/B is about 0.52 uM-7.13 uM， the evidence of safety and efficacy of zd-5 were observed and confirmed by experimental animals suffered from the flu in the work as well. On the other hand, there are only a few effective antiviral drugs available for the prophylactic or therapeutic treatment of the highly contagious SARS-CoV-2 in humans. Target-based virtual screening of Dryopteris with LC/MS guidance was applied to identify the novel and high-content compounds with inhibitory effects on SARS-CoV-2 in Vero E6 cells from the plant Dryopteris wallichiana. The inhibition assay of targets showed that compound 3 mainly inhibited SARS-CoV-2 3CLpro, with effective test values. This study has led to the development of zd-5 and compound 3-4 for exploring and designing inhibitors for the Flu virus and SARS-CoV-2.
语种	中文
	2022-04
学位授予单位	中国科学院大学
文献类型	学位论文
条目标识符	http://ir.kib.ac.cn/handle/151853/75141
专题	昆明植物所硕博研究生毕业学位论文
推荐引用方式 GB/T 7714	侯博. 基于酚酸类结构研究抗流感病毒、新冠病毒前体药物[D]. 中国科学院大学,2022.

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