Inhibition of SARS-CoV 3CL protease by flavonoids
Inhibition of SARS-CoV 3CL protease by flavonoids
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DOI：
10.1080/14756366.2019.1690480
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发表时间：
2020-01-01
影响因子：
5.6
通讯作者：
Kim, Mi-Sun
中科院分区：
文献类型：
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作者：
Jo, Seri;Kim, Suwon;Kim, Mi-Sun
严重急性呼吸综合征（SARS）和中东呼吸综合征-冠状病毒引起了严重恐慌。因此，需要针对这些病毒的研究。冠状病毒（Coronaviruses，CoV）已成为类黄酮类化合物的靶标。一些黄酮类化合物对CoV的抗病毒活性推测是通过抑制3C样蛋白酶（3CLpro）直接引起的。在这里，我们应用黄酮类化合物库系统地探测对SARS-CoV 3CLpro的抑制化合物。发现Herbacetin、rhoifolin和pectolinarin有效地阻断SARS-CoV 3CLpro的酶活性。三种黄酮类化合物的相互作用也通过荧光法得到了证实。诱导对接分析表明，S1，S2和S3 '位点参与与黄酮类化合物的结合。与之前研究的比较表明，Triton X-100在反对假阳性或高估黄酮类化合物的抑制活性方面发挥了关键作用。通过系统分析，提出三种黄酮类化合物可作为模板设计功能改进的抑制剂。
There were severe panics caused by Severe Acute Respiratory Syndrome (SARS) and Middle-East Respiratory Syndrome-Coronavirus. Therefore, researches targeting these viruses have been required. Coronaviruses (CoVs) have been rising targets of some flavonoids. The antiviral activity of some flavonoids against CoVs is presumed directly caused by inhibiting 3C-like protease (3CLpro). Here, we applied a flavonoid library to systematically probe inhibitory compounds against SARS-CoV 3CLpro. Herbacetin, rhoifolin and pectolinarin were found to efficiently block the enzymatic activity of SARS-CoV 3CLpro. The interaction of the three flavonoids was confirmed using a tryptophan-based fluorescence method, too. An induced-fit docking analysis indicated that S1, S2 and S3 ' sites are involved in binding with flavonoids. The comparison with previous studies showed that Triton X-100 played a critical role in objecting false positive or overestimated inhibitory activity of flavonoids. With the systematic analysis, the three flavonoids are suggested to be templates to design functionally improved inhibitors.