Rahman Fazlur, Tabrez Shams, Ali Rahat, Alqahtani Ali S, Ahmed Mohammad Z, Rub Abdur
Infection and Immunity Lab (414), Department of Biotechnology, Jamia Millia Islamia (A Central University), New Delhi, 110025, India.
King Saud University College of Pharmacy, Department of Pharmacognosy, Riyadh, 11451, Saudi Arabia.
J Tradit Complement Med. 2021 Mar;11(2):173-179. doi: 10.1016/j.jtcme.2021.01.006. Epub 2021 Jan 22.
COVID-19 emerged by the end of 2019 in Wuhan, China. It spreaded and became a public health emergency all over the world by mid of April 2020. Flavonoids are specialized metabolites that have antimicrobial properties including anti-viral activity. Rutin, a medicinally important flavonoid belongs to one of the best natural antioxidant classes. It has antiprotozoal, antibacterial, and antiviral properties. Keeping the antimicrobial potential of rutin in mind, we studied its role in the inhibition of essential proteins of SARS-CoV-2 including main protease (M), RNA-dependent RNA polymerase (RdRp), papain-like protease (PL), and spike (S)-protein through different approaches.
Molecular docking, inhibition constant, hydrogen bond calculations, and ADMET-properties prediction were performed using different softwares.
Molecular docking study showed significant binding of rutin with M, RdRp, PL, and S-proteins of SARS-CoV-2. Out of these four proteins, M exhibited the strongest binding affinity with the least binding energy (-8.9 kcal/mol) and stabilized through hydrogen bonds with bond lengths ranging from 1.18 Å to 3.17 Å as well as hydrophobic interactions. The predicted ADMET and bioactivity showed its optimal solubility, non-toxic, and non-carcinogenic properties. The values of the predicted inhibitory constant of the rutin with SARS-CoV-2 vital proteins ranged between 5.66 μM and 6.54 μM which suggested its promising drug candidature. This study suggested rutin alone or in combination as a dietary supplement may be used to fight against COVID-19 after detailed and studies.
2019年末新型冠状病毒肺炎（COVID-19）在中国武汉出现。到2020年4月中旬，它已传播并成为全球公共卫生突发事件。类黄酮是具有抗菌特性（包括抗病毒活性）的特殊代谢产物。芦丁是一种具有重要药用价值的类黄酮，属于最佳天然抗氧化剂类别之一。它具有抗原生动物、抗菌和抗病毒特性。考虑到芦丁的抗菌潜力，我们通过不同方法研究了其在抑制严重急性呼吸综合征冠状病毒2（SARS-CoV-2）必需蛋白中的作用，这些蛋白包括主蛋白酶（M）、RNA依赖性RNA聚合酶（RdRp）、木瓜样蛋白酶（PL）和刺突（S）蛋白。
使用不同软件进行分子对接、抑制常数、氢键计算和药物代谢动力学（ADMET）性质预测。
分子对接研究表明芦丁与SARS-CoV-2的M、RdRp、PL和S蛋白有显著结合。在这四种蛋白质中，M表现出最强的结合亲和力，结合能最低（-8.9千卡/摩尔），并通过键长在1.18 Å至3.17 Å之间的氢键以及疏水相互作用得以稳定。预测的ADMET和生物活性表明其具有最佳的溶解性、无毒和非致癌特性。芦丁与SARS-CoV-2重要蛋白的预测抑制常数在5.66 μM至6.54 μM之间，这表明其作为有前景的药物候选物。本研究表明，经过详细研究后，单独使用芦丁或与其他物质联合作为膳食补充剂可能可用于对抗COVID-19。
