Virtual screening and repurposing of FDA approved drugs against COVID-19 main protease
Virtual screening and repurposing of FDA approved drugs against COVID-19 main protease
复制标题
DOI：
10.1016/j.lfs.2020.117627
复制
发表时间：
2020-06-15
期刊：
影响因子：
6.1
通讯作者：
Al-Nazawi, Mohammed
中科院分区：
文献类型：
--
作者：
Kandeel, Mahmoud;Al-Nazawi, Mohammed
目的：2019年12月，中国武汉出现了2019年冠状病毒病（COVID-19）病毒。在这项研究中，第一个解析的COVID-19晶体结构（主要蛋白酶）是通过FDA批准的药物数据集进行虚拟筛选研究的目标。此外，通过序列统计学和遗传学的研究，弥补了COVID-19与先前已知的致命冠状病毒（CoV）流行病SARS和MERS CoV之间关系的知识空白。材料和方法：对COVID-19主要蛋白酶的分子建模、虚拟筛选、对接、序列比较统计和遗传学进行了研究。COVID-19 Mpro与SARS CoV形成了一个系统发育组，与MERS CoV距离较远。COVID-19/SARS和COVID-19/MERS CoV序列比较的同一性%分别为96.061和51.61。虚拟筛选研究中的前20种药物包括一种广谱抗病毒药（利巴韦林）、抗B型肝炎病毒（替比夫定）、两种维生素（维生素B12和烟酰胺）和其他各种全身作用药物。特别令人感兴趣的是，利巴韦林已被用于治疗SARS CoV病例。意义：本研究提供了Mpro的第一个解析的COVID + 19结构的全面靶向，并找到了一种合适的保存药物，用于重新利用抗病毒Mpro。利巴韦林、替比夫定、维生素B12和烟酰胺可联合用于COVID治疗。这项举措重新定位了已经上市和批准的安全药物，用于COVID治疗的潜在用途。
Aims: In December 2019, the Coronavirus disease-2019 (COVID-19) virus has emerged in Wuhan, China. In this research, the first resolved COVID-19 crystal structure (main protease) was targeted in a virtual screening study by of FDA approved drugs dataset. In addition, a knowledge gap in relations of COVID-19 with the previously known fatal Coronaviruses (CoVs) epidemics, SARS and MERS CoVs, was covered by investigation of sequence statistics and phylogenetics.Materials and methods: Molecular modeling, virtual screening, docking, sequence comparison statistics and phylogenetics of the COVID-19 main protease were investigated.Keyfindings: COVID-19 Mpro formed a phylogenetic group with SARS CoV that was distant from MERS CoV. The identity% was 96.061 and 51.61 for COVID-19/SARS and COVID-19/MERS CoV sequence comparisons, respectively. The top 20 drugs in the virtual screening studies comprised a broad-spectrum antiviral (ribavirin), anti-hepatitis B virus (telbivudine), two vitamins (vitamin B12 and nicotinamide) and other miscellaneous systemically acting drugs. Of special interest, ribavirin had been used in treating cases of SARS CoV.Significance: The present study provided a comprehensive targeting of the first resolved COVID + 19 structure of Mpro and found a suitable save drugs for repurposing against the viral Mpro. Ribavirin, telbivudine, vitamin B12 and nicotinamide can be combined and used for COVID treatment. This initiative relocates already marketed and approved safe drugs for potential use in COVID-treatment.