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基于肽的肠道病毒 71 3C 蛋白酶共价抑制剂的抗病毒活性。

Antiviral activities of peptide-based covalent inhibitors of the Enterovirus 71 3C protease.

机构信息

Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), 61 Biopolis Drive, Proteos #06-05, 138673, Singapore.

Experimental Therapeutics Centre, Agency for Science, Technology and Research (A*STAR), 31 Biopolis Way, Nanos #03-01, 138669, Singapore.

出版信息

Sci Rep. 2016 Sep 20;6:33663. doi: 10.1038/srep33663.

DOI:10.1038/srep33663
PMID:27645381
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5028882/
Abstract

Hand, Foot and Mouth Disease is a highly contagious disease caused by a range of human enteroviruses. Outbreaks occur regularly, especially in the Asia-Pacific region, putting a burden on public healthcare systems. Currently, there is no antiviral for treating this infectious disease and the only vaccines are limited to circulation in China, presenting an unmet medical need that needs to be filled urgently. The human enterovirus 3 C protease has been deemed a plausible drug target due to its essential roles in viral replication. In this study, we designed and synthesized 10 analogues of the Rhinovirus 3 C protease inhibitor, Rupintrivir, and tested their 3 C protease inhibitory activities followed by a cellular assay using human enterovirus 71 (EV71)-infected human RD cells. Our results revealed that a peptide-based compound containing a trifluoromethyl moiety to be the most potent analogue, with an EC50 of 65 nM, suggesting its potential as a lead for antiviral drug discovery.

摘要

手足口病是一种由多种人类肠道病毒引起的高度传染性疾病。疫情时有发生，特别是在亚太地区，给公共卫生系统带来了负担。目前，尚无针对这种传染病的抗病毒药物，而唯一的疫苗仅限于在中国流通，这是一个亟待满足的未满足的医疗需求。人肠道病毒 3C 蛋白酶因其在病毒复制中的重要作用而被认为是一种合理的药物靶点。在这项研究中，我们设计并合成了 10 种鼻病毒 3C 蛋白酶抑制剂 Rupintrivir 的类似物，并测试了它们对 3C 蛋白酶的抑制活性，然后用人肠道病毒 71（EV71）感染的人 RD 细胞进行了细胞测定。结果表明，含有三氟甲基的肽类化合物是最有效的类似物，EC50 为 65nM，提示其具有作为抗病毒药物发现的先导化合物的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07ca/5028882/86306fb715ce/srep33663-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07ca/5028882/df102642725a/srep33663-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07ca/5028882/38800e9a3e06/srep33663-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07ca/5028882/987ae1c175d6/srep33663-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07ca/5028882/86306fb715ce/srep33663-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07ca/5028882/df102642725a/srep33663-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07ca/5028882/38800e9a3e06/srep33663-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07ca/5028882/987ae1c175d6/srep33663-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07ca/5028882/86306fb715ce/srep33663-f4.jpg

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