Abdallah Hossam M, El-Halawany Ali M, Sirwi Alaa, El-Araby Amr M, Mohamed Gamal A, Ibrahim Sabrin R M, Koshak Abdulrahman E, Asfour Hani Z, Awan Zuhier A, A Elfaky Mahmoud
Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
Pharmaceuticals (Basel). 2021 Mar 4;14(3):213. doi: 10.3390/ph14030213.
The emergence of the SARS-CoV-2 pandemic has prompted scientists to search for an efficient antiviral medicine to overcome the rapid spread and the marked increase in the number of patients worldwide. In this regard natural products could be a potential source of substances active against coronavirus infections. A systematic computer-aided virtual screening approach was carried out using commercially available natural products found on the Zinc Database in addition to an in-house compound library to identify potential natural product inhibitors of SARS-CoV-2 main protease (M). The top eighteen hits from the screening were selected for in vitro evaluation on the viral protease (SARS-CoV-2 M). Five compounds (naringenin, 2,3',4,5',6-pentahydroxybenzophenone, apigenin-7--glucoside, sennoside B, and acetoside) displayed high activity against the viral protein. Acteoside showed similar activity to the positive control GC376. The most potent compounds were tested in vitro on SARS-CoV-2 Egyptian strain where only naringenin showed moderate anti-SARS-CoV-2 activity at non-cytotoxic micromolar concentrations in vitro with a significant selectivity index (CC/IC = 178.748/28.347 = 6.3). Moreover; a common feature pharmacophore model was generated to explain the requirements for enzyme inhibition by this diverse group of active ligands. These results pave a path for future repurposing and development of natural products to aid in the battle against COVID-19.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）大流行的出现促使科学家们寻找一种有效的抗病毒药物，以克服其在全球范围内的快速传播和患者数量的显著增加。在这方面，天然产物可能是对抗冠状病毒感染的活性物质的潜在来源。除了一个内部化合物库外，还使用锌数据库中可商购的天然产物进行了系统的计算机辅助虚拟筛选方法，以鉴定SARS-CoV-2主要蛋白酶（M）的潜在天然产物抑制剂。从筛选中选出排名前18的命中物，对病毒蛋白酶（SARS-CoV-2 M）进行体外评估。五种化合物（柚皮素、2,3',4,5',6-五羟基二苯甲酮、芹菜素-7-O-葡萄糖苷、番泻苷B和乙酰化侧柏叶苷）对病毒蛋白显示出高活性。毛蕊花糖苷显示出与阳性对照GC376相似的活性。在体外对SARS-CoV-2埃及株测试了最有效的化合物，其中只有柚皮素在非细胞毒性微摩尔浓度下显示出中等的抗SARS-CoV-2活性，且具有显著的选择性指数（CC/IC = 178.748/28.347 = 6.3）。此外，生成了一个共同特征药效团模型，以解释这一不同组的活性配体对酶抑制的要求。这些结果为未来天然产物的重新利用和开发铺平了道路，以帮助对抗2019冠状病毒病。
