Frimayanti Neni, Ikhtiarudin Ihsan, Ardiyansyah Roni, Utami Rahayu, Septama Abdi Wira
Department of Pharmacy, Sekolah Tinggi Ilmu Farmasi Riau, Jalan Kamboja, Simpang Baru, Pekanbaru, 28293 Indonesia.
Research Centre for Pharmaceutical Ingredients and Traditional Medicine- BRIN, KST BJ Habibie, Setu, 15314 Tanggerang Selatan Indonesia.
In Silico Pharmacol. 2025 May 31;13(2):78. doi: 10.1007/s40203-025-00368-8. eCollection 2025.
Flavonoids possess various biological activities, including the ability to inhibit SARS-CoV-2. This study aimed to synthesize 3',4'-dimethoxyflavonol (F34) and assess its potential as an anti-SARS-CoV-2 agent. F34 was synthesized using the Flynn-Algar-Oyamada reaction, and molecular docking studies were performed using the MOE 2022.02 software, utilizing the SARS-CoV-2 crystal structure (PDB ID: 6M2N) from the RCSB Protein Data Bank. To further investigate the binding stability of F34, pharmacophore analysis and molecular dynamics (MD) simulations were conducted. The synthesis yielded F34 at 75.23% yield, as confirmed by 1 H-NMR, FT-IR, and UV-Vis analyses. Docking results indicated that F34 interacted with key amino acid residues in the SARS-CoV-2 active site, with a binding free energy of -8.42 kcal/mol and an RMSD of 1.03. F34 forms a hydrogen bond with Gly143 and His164, and interacts with the catalytic dyad residues His41 and Cys145, which are crucial for SARS-CoV-2 inhibition. MD simulations further suggested stable hydrogen-bond interactions between F34 and Gly143/His164 at distances below 2.9 Å. These findings suggest that F34 could be a promising SARS-CoV-2 inhibitor.
The online version contains supplementary material available at 10.1007/s40203-025-00368-8.
类黄酮具有多种生物活性，包括抑制严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的能力。本研究旨在合成3'，4'-二甲氧基黄酮醇（F34）并评估其作为抗SARS-CoV-2药物的潜力。使用弗林-阿尔加-小山田反应合成了F34，并使用MOE 2022.02软件进行分子对接研究，利用来自RCSB蛋白质数据库的SARS-CoV-2晶体结构（PDB ID：6M2N）。为了进一步研究F34的结合稳定性，进行了药效团分析和分子动力学（MD）模拟。经1H-NMR、FT-IR和UV-Vis分析证实，合成得到的F34产率为75.23%。对接结果表明，F34与SARS-CoV-2活性位点中的关键氨基酸残基相互作用，结合自由能为-8.42 kcal/mol，均方根偏差（RMSD）为1.03。F34与Gly143和His164形成氢键，并与对SARS-CoV-2抑制至关重要的催化二元残基His41和Cys145相互作用。MD模拟进一步表明，F34与Gly143/His164之间在距离低于2.9 Å时存在稳定的氢键相互作用。这些发现表明F34可能是一种有前景的SARS-CoV-2抑制剂。
在线版本包含可在10.1007/s40203-025-00368-8获取的补充材料。
