Shaaban Saad, Abdou Aly, Alhamzani Abdulrahman G, Abou-Krisha Mortaga M, Al-Qudah Mahmoud A, Alaasar Mohamed, Youssef Ibrahim, Yousef Tarek A
Department of Chemistry, College of Science, King Faisal University, Al-Ahsa 31982, Saudi Arabia.
Department of Chemistry, Faculty of Science, Mansoura University, Mansoura 35516, Egypt.
Life (Basel). 2023 Mar 30;13(4):912. doi: 10.3390/life13040912.
Since the first report of the organoselenium compound, ebselen, as a potent inhibitor of the SARS-CoV-2 M main protease by Z. Jin et al. (Nature, 2020), different OSe analogs have been developed and evaluated for their anti-COVID-19 activities. Herein, organoselenium-clubbed Schiff bases were synthesized in good yields (up to 87%) and characterized using different spectroscopic techniques. Their geometries were studied by DFT using the B3LYP/6-311 (d, p) approach. Ten FDA-approved drugs targeting COVID-19 were used as model pharmacophores to interpret the binding requirements of COVID-19 inhibitors. The antiviral efficiency of the novel organoselenium compounds was assessed by molecular docking against the 6LU7 protein to investigate their possible interactions. Our results showed that the COVID-19 primary protease bound to organoselenium ligands with high binding energy scores ranging from -8.19 to -7.33 Kcal/mol for and to -6.10 to -6.20 Kcal/mol for and . Furthermore, the docking data showed that and are good M inhibitors. Moreover, the drug-likeness studies, including Lipinski's rule and ADMET properties, were also assessed. Interestingly, the organoselenium candidates manifested solid pharmacokinetic qualities in the ADMET studies. Overall, the results demonstrated that the organoselenium-based Schiff bases might serve as possible drugs for the COVID-19 epidemic.
自Z. Jin等人（《自然》，2020年）首次报道有机硒化合物依布硒啉作为严重急性呼吸综合征冠状病毒2（SARS-CoV-2）M主蛋白酶的强效抑制剂以来，已开发并评估了不同的OSe类似物的抗2019冠状病毒病（COVID-19）活性。在此，以良好的产率（高达87%）合成了有机硒结合的席夫碱，并使用不同的光谱技术对其进行了表征。采用密度泛函理论（DFT）的B3LYP/6-311（d, p）方法研究了它们的几何结构。使用10种美国食品药品监督管理局（FDA）批准的针对COVID-19的药物作为模型药效团来解释COVID-19抑制剂的结合要求。通过对6LU7蛋白进行分子对接评估了新型有机硒化合物的抗病毒效率，以研究它们可能的相互作用。我们的结果表明，COVID-19主要蛋白酶与有机硒配体结合，结合能得分较高，对于[具体化合物1]和[具体化合物2]为-8.19至-7.33千卡/摩尔，对于[具体化合物[X]]和[具体化合物[Y]]为-6.10至-6.20千卡/摩尔。此外，对接数据表明[具体化合物1]和[具体化合物2]是良好的M蛋白酶抑制剂。此外，还评估了包括Lipinski规则和药物代谢及毒性性质（ADMET）等类药性质研究。有趣的是，有机硒候选物在ADMET研究中表现出良好的药代动力学性质。总体而言，结果表明基于有机硒的席夫碱可能成为治疗COVID-19疫情的潜在药物。
