Alsafi Mona A, Hughes David L, Said Musa A
Chemistry Department, College of Science, Taibah University, PO Box 30002, Al-Madinah Al Munawarah, Code 1417, Saudi Arabia.
School of Chemistry, University of East Anglia, Norwich NR4 7TJ, England.
Acta Crystallogr C Struct Chem. 2020 Dec 1;76(Pt 12):1043-1050. doi: 10.1107/S2053229620014217. Epub 2020 Nov 5.
The first example of molecular docking of the SARS-CoV-2 main protease for COVID-19 [M, Protein Data Bank (PDB) code 7BQY] by a chalcone-based ligand, namely, (E)-1-(2,4-dichlorophenyl)-3-[4-(morpholin-4-yl)phenyl]prop-2-en-1-one, CHClNO, I, is presented. Two-dimensional (2D) LIGPLOT representations calculated for the inhibitor N3, viz. N-{[(5-methylisoxazol-3-yl)carbonyl]alanyl}-L-valyl-N-((1R,2Z)-4-(benzyloxy)-4-oxo-1-{[(3R)-2-oxopyrrolidin-3-yl]methyl}but-2-enyl)-L-leucinamide, and 7BQY are included for comparison with our chalcone-based complexes. The binding affinity of our chalcone ligand with 7BQY is -7.0 kcal mol, a high value which was attributed to the presence of a hydrogen bond, together with many hydrophobic interactions between the drug and the active amino acid residues of the receptor. Docking studies were also performed, employing rigid and flexible binding modes for the ligand. The superposition of N3 and the chalcone docked into the binding pocket of 7BQY is also presented. The synthesis, single-crystal structure, Hirshfeld surface analysis (HSA) and spectral characterization of heterocyclic chalcone-based compound I, are also presented. The molecules are stacked, with normal π-π interactions, in the crystal.
本文展示了首个基于查尔酮的配体，即(E)-1-(2,4-二氯苯基)-3-[4-(吗啉-4-基)苯基]丙-2-烯-1-酮（CHClNO，I）与严重急性呼吸综合征冠状病毒2（SARS-CoV-2）主要蛋白酶（用于治疗2019冠状病毒病，[M，蛋白质数据库（PDB）代码7BQY]）进行分子对接的实例。文中还给出了针对抑制剂N3（即N-{[(5-甲基异恶唑-3-基)羰基]丙氨酰}-L-缬氨酰-N-((1R,2Z)-4-(苄氧基)-4-氧代-1-{[(3R)-2-氧代吡咯烷-3-基]甲基}丁-2-烯基)-L-亮氨酰胺）和7BQY计算得到的二维（2D）LIGPLOT表示，以便与我们基于查尔酮的复合物进行比较。我们的查尔酮配体与7BQY的结合亲和力为-7.0 kcal mol，这一高值归因于存在氢键以及药物与受体活性氨基酸残基之间的许多疏水相互作用。还采用配体的刚性和柔性结合模式进行了对接研究。文中还展示了N3与对接至7BQY结合口袋中的查尔酮的叠加情况。本文还介绍了基于杂环查尔酮的化合物I的合成、单晶结构、 Hirshfeld表面分析（HSA）和光谱表征。在晶体中，分子通过正常的π-π相互作用堆叠在一起。
