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.

译文

:严重急性呼吸系统综合症(SARS)和中东呼吸系统综合症-冠状病毒引起严重恐慌。因此,需要针对这些病毒的研究。冠状病毒(CoV)已成为某些类黄酮的上升靶标。推测某些类黄酮对CoV的抗病毒活性直接由抑制3C样蛋白酶(3CLpro)引起。在这里,我们应用了类黄酮库来系统地探测针对SARS-CoV 3CLpro的抑制性化合物。已发现草乙素,rhoifolin和果胶素可有效阻断SARS-CoV 3CLpro的酶活性。也使用基于色氨酸的荧光方法确认了三种类黄酮的相互作用。诱导拟合对接分析表明,S1,S2和S3'位点与类黄酮结合。与先前研究的比较表明,Triton X-100在反对类黄酮的假阳性或高估抑制活性中发挥了关键作用。通过系统的分析,建议将这三种类黄酮作为模板来设计功能改进的抑制剂。

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