Laboratory of Computational Simulations (LabIn02), Institute of Educational Sciences, Federal University of Western Pará, Santarém 68040-255, Pará, Brazil.
Instituto de Química, Universidade de Brasília, Brasília 70910-900, Distrito Federal, Brazil.
Int J Mol Sci. 2023 Oct 12;24(20):15113. doi: 10.3390/ijms242015113.
Understanding the role of 3CLpro protease for SARS-CoV-2 replication and knowing the potential of flavonoid molecules like rutin, myricetin, and baicalein against 3CLpro justify an investigation into their inhibition. This study investigates possible bonds and reactivity descriptors of rutin, myricetin, and baicalein through conformational and electronic properties. Density functional theory was used to determine possible interactions. Analyses were carried out through the molecular electrostatic potential, electron localization function, Fukui function descriptors based on frontier orbitals, and non-covalent interactions. A docking study was performed using a resolution of 1.55 Å for 3CLpro to analyze the interactions of rutin, myricetin, and baicalein. Scores of structures showed that rutin is the best ligand, followed by myricetin and baicalein. Docking studies showed that baicalein and rutin can establish effective interactions with residues of the catalytic dyad (Cys145 and His41), but just rutin forms a hydrogen bond. Myricetin, in turn, could not establish an effective interaction with Cys145. Baicalein interaction arose with active residues such as Arg188, Val186, Gln189, and Gln192. Interactions of rutin and myricetin with Arg188 and Gln189 were also found. A critical interaction was observed only for rutin with the hydroxyls of ring A with His41, and also for Cys145 with rings B and C, which is probably related to the highest score of rutin.
了解 3CLpro 蛋白酶在 SARS-CoV-2 复制中的作用，以及了解芦丁、杨梅素和黄芩素等类黄酮分子对 3CLpro 的潜在抑制作用， justifies 对其进行抑制研究。本研究通过构象和电子特性来研究芦丁、杨梅素和黄芩素的可能键合和反应性描述符。使用密度泛函理论来确定可能的相互作用。通过分子静电势、电子定域函数、基于前线轨道的福井函数描述符和非共价相互作用进行分析。使用 1.55Å 的分辨率对 3CLpro 进行对接研究，以分析芦丁、杨梅素和黄芩素的相互作用。结构得分表明，芦丁是最好的配体，其次是杨梅素和黄芩素。对接研究表明，黄芩素和芦丁可以与催化二联体（Cys145 和 His41）的残基建立有效相互作用，但只有芦丁形成氢键。另一方面，杨梅素不能与 Cys145 建立有效相互作用。黄芩素与活性残基如 Arg188、Val186、Gln189 和 Gln192 相互作用。还发现芦丁和杨梅素与 Arg188 和 Gln189 的相互作用。只有芦丁与 His41 的 A 环上的羟基以及 Cys145 与 B 环和 C 环的关键相互作用，这可能与芦丁的最高得分有关。
