菲啶类抗PEDV与SARS-CoV-2的活性化合物设计与作用机制研究

	菲啶类抗PEDV与SARS-CoV-2的活性化合物设计与作用机制研究; Design and mechanism of active compounds of phenanthridines against PEDV and SARS-CoV-2
	王宜挺
导师	郝小江
摘要	Coronavirus is a type of positive-stranded RNA virus with the largest genome. We explored the anti-PEDV effects of several phenanthridine-type molecules, which could inhibit multiple viruses by down-regulating the expression of host Hsc70. In order to obtain more active molecules, the structure modification of active molecules was carried out. Based on the research basis of coronavirus and phenanthridine molecules, we launched a drug discovery study targeting SARS-CoV-2 nucleocapsid protein and main protease when SARS-CoV-2 is pandemic during the research process. The first chapter described a research on designing and synthesising of PEDV inhibitors targeting host Hsc70. And 69 derivatives were synthesized. A type of phenanthridone molecule with methoxy substitution at the 4th position and a heterocyclic fragment at the 8th and 9th positions was discovered. These molecules have excellent anti-PEDV activity and retain the ability to down-regulate the host Hsc70. The result provides a new class of anti-PEDV drugs. As the compounds with a broad-spectrum antiviral mechanism, it is possible to act on more coronaviruse. The second chapter described a research on designing and synthesising of SARS-CoV-2 inhibitors. Based on the reported coronavirus nucleocapsid inhibitor PJ34, 19 derivatives were designed and synthesized. And compound 70 stands out in the screening of SPR assay. The Dissociation constant with SARS-CoV-2 nucleocapsid protein was 7.8 μM, compared with the PJ34, the activity is increased by nearly 90 times. Learn from the " drug repositioning strategy", a virtual screening based on the main protease was carried out. And compounds 41 and 67 with good inhibitory activity against the main protease were obtained. They showed 85.6% and 71.6% inhibition rates, respectively. The result provides some clues for SARS-CoV-2 drug discovery. The third chapter reviewed the inhibitors of PEDV, their structures and tagets were summarized. And we also made an outlook on the drug discovery of anti-PEDV.
	2021-05
文献类型	学位论文
条目标识符	http://ir.kib.ac.cn/handle/151853/74530
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	王宜挺. 菲啶类抗PEDV与SARS-CoV-2的活性化合物设计与作用机制研究, Design and mechanism of active compounds of phenanthridines against PEDV and SARS-CoV-2[D],2021.

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