A screen of the NIH Clinical Collection small molecule library identifies potential anti-coronavirus drugs.
A screen of the NIH Clinical Collection small molecule library identifies potential anti-coronavirus drugs.
复制标题
DOI：
10.1016/j.antiviral.2014.11.010
复制
发表时间：
2015-03
影响因子：
7.6
通讯作者：
Zhang X
中科院分区：
文献类型：
--
作者：
Cao J;Forrest JC;Zhang X
高通量筛选确定了NCC库中727种药物中的84种具有抗冠状病毒作用。结果显示，51种候选药物阻断病毒进入，而另外19种抑制病毒复制。高三尖杉酯碱被发现是对抗动物和人类冠状病毒最有效的抑制剂。随着最近中东呼吸综合征冠状病毒在人类中的出现和毁灭性猪流行性腹泻冠状病毒在猪中的爆发，迫切需要治疗干预。然而，目前还没有抗冠状病毒药物。为了帮助快速开发抗冠状病毒药物，我们在细胞培养中使用表达荧光素酶的重组鼠冠状病毒筛选NIH临床保藏中心。在筛选的727种化合物中，发现84种具有显著的抗冠状病毒作用。进一步的实验显示，51种化合物阻断了病毒进入，而另外19种化合物抑制了病毒复制。对前3种抑制剂（六氯虫胺、硝唑尼特和高三尖杉酯碱）的其他验证研究表明，其具有强大的抗冠状病毒活性（病毒滴度降低6至8 log10），IC 50范围为11 nM至1.2 μM。此外，高三尖杉酯碱和六氯酚对不同种类的人类和动物冠状病毒表现出广泛的抗病毒活性。由于NIH Clinical Collection包含已经通过临床试验的化合物，因此这些小分子抑制剂具有作为抗冠状病毒药物快速开发的巨大潜力。
High-throughput screening identified 84 of the 727 drugs in the NCC library to have anti-coronavirus effect. Results revealed that 51 candidate drugs blocked virus entry while 19 others inhibited viral replication. Homoharringtonine was found to be the most potent inhibitor against animal and human coronaviruses. With the recent emergence of Middle East Respiratory Syndrome coronavirus in humans and the outbreak of devastating porcine epidemic diarrhea coronavirus in swine, therapeutic intervention is urgently needed. However, anti-coronavirus drugs currently are not available. In an effort to assist rapid development of anti-coronavirus drugs, here we screened the NIH Clinical Collection in cell culture using a luciferase reporter-expressing recombinant murine coronavirus. Of the 727 compounds screened, 84 were found to have a significant anti-coronavirus effect. Further experiments revealed that 51 compounds blocked virus entry while 19 others inhibited viral replication. Additional validation studies with the top 3 inhibitors (hexachlorophene, nitazoxanide and homoharringtonine) demonstrated robust anti-coronavirus activities (a reduction of 6 to 8 log10 in virus titer) with an IC50 ranging from 11 nM to 1.2 μM. Furthermore, homoharringtonine and hexachlorophene exhibited broad antiviral activity against diverse species of human and animal coronaviruses. Since the NIH Clinical Collection consists of compounds that have already been through clinical trials, these small molecule inhibitors have a great potential for rapid development as anti-coronavirus drugs.
登录
查看更多内容
影响因子：
--
作者：
Andruska, Neal;Mao, Chengjian;Shapiro, David J.
通讯作者：
Shapiro, David J.
DOI：
10.1016/j.str.2005.08.021
发表时间：
2005-12
期刊：
Structure (London, England : 1993)
影响因子：
--
作者：
Fan H;Ooi A;Tan YW;Wang S;Fang S;Liu DX;Lescar J
通讯作者：
Lescar J
增强的绿色荧光蛋白表达可用于监测体外和小鼠中枢神经系统中鼠冠状病毒的扩散。
影响因子：
3.2
作者：
Das Sarma J;Scheen E;Seo SH;Koval M;Weiss SR
通讯作者：
Weiss SR
影响因子：
5.4
作者：
Das Sarma, J;Fu, L;Lavi, E
通讯作者：
Lavi, E
影响因子：
7.6
作者：
Kim SM;Park JH;Lee KN;Kim SK;Ko YJ;Lee HS;Cho IS
通讯作者：
Cho IS