Antonopoulou Io, Sapountzaki Eleftheria, Rova Ulrika, Christakopoulos Paul
Biochemical Process Engineering, Division of Chemical Engineering, Department of Civil, Environmental and Natural Resources Engineering, Luleå University of Technology, SE-97187 Luleå, Sweden.
Biomedicines. 2022 Jul 25;10(8):1787. doi: 10.3390/biomedicines10081787.
The main protease (M) of SARS-CoV-2 is an appealing target for the development of antiviral compounds, due to its critical role in the viral life cycle and its high conservation among different coronaviruses and the continuously emerging mutants of SARS-CoV-2. Ferulic acid (FA) is a phytochemical with several health benefits that is abundant in plant biomass and has been used as a basis for the enzymatic or chemical synthesis of derivatives with improved properties, including antiviral activity against a range of viruses. This study tested 54 reported FA derivatives for their inhibitory potential against M by in silico simulations. Molecular docking was performed using Autodock Vina, resulting in comparable or better binding affinities for 14 compounds compared to the known inhibitors N3 and GC376. ADMET analysis showed limited bioavailability but significantly improved the solubility for the enzymatically synthesized hits while better bioavailability and druglikeness properties but higher toxicity were observed for the chemically synthesized ones. MD simulations confirmed the stability of the complexes of the most promising compounds with M, highlighting FA rutinoside and compound e27 as the best candidates from each derivative category.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的主要蛋白酶（M）是开发抗病毒化合物的一个有吸引力的靶点，因为它在病毒生命周期中起着关键作用，并且在不同冠状病毒以及SARS-CoV-2不断出现的突变体中具有高度保守性。阿魏酸（FA）是一种具有多种健康益处的植物化学物质，在植物生物质中含量丰富，并已被用作酶促或化学合成具有改进特性（包括对多种病毒的抗病毒活性）的衍生物的基础。本研究通过计算机模拟测试了54种已报道的FA衍生物对M的抑制潜力。使用Autodock Vina进行分子对接，结果显示与已知抑制剂N3和GC376相比，14种化合物具有相当或更好的结合亲和力。ADMET分析表明生物利用度有限，但酶促合成的命中化合物的溶解度显著提高，而化学合成的化合物则具有更好的生物利用度和类药性质，但毒性更高。分子动力学模拟证实了最有前景的化合物与M形成的复合物的稳定性，突出了阿魏酸芸香苷和化合物e27作为每个衍生物类别的最佳候选物。
