Department of Biomedical Sciences, College of Veterinary Medicine, King Faisal University, Al-hofuf, 31982, Al-ahsa, Saudi Arabia; Department of Pharmacology, Faculty of Veterinary Medicine, Kafrelshikh University, Kafrelshikh 33516, Egypt.
Department of Biomedical Sciences, College of Veterinary Medicine, King Faisal University, Al-hofuf, 31982, Al-ahsa, Saudi Arabia.
Life Sci. 2020 Jun 15;251:117627. doi: 10.1016/j.lfs.2020.117627. Epub 2020 Apr 3.
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.
Molecular modeling, virtual screening, docking, sequence comparison statistics and phylogenetics of the COVID-19 main protease were investigated.
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.
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.
2019 年 12 月，新型冠状病毒病-2019（COVID-19）病毒在中国武汉出现。在这项研究中，针对第一个已解析的 COVID-19 晶体结构（主要蛋白酶），我们进行了虚拟筛选研究，使用的是美国食品和药物管理局批准药物数据集。此外，通过调查序列统计和系统发育学，弥补了 COVID-19 与先前已知致命冠状病毒（CoVs）SARS 和 MERS CoV 之间关系的知识空白。
研究了 COVID-19 主要蛋白酶的分子建模、虚拟筛选、对接、序列比较统计和系统发育学。
COVID-19 Mpro 与 SARS CoV 形成了一个进化群，与 MERS CoV 相距较远。COVID-19/SARS 和 COVID-19/MERS CoV 序列比较的身份百分比分别为 96.061%和 51.61%。虚拟筛选研究中排名前 20 的药物包括广谱抗病毒药物（利巴韦林）、抗乙型肝炎病毒药物（替比夫定）、两种维生素（维生素 B12 和烟酰胺）和其他全身性作用的药物。特别值得注意的是，利巴韦林曾用于治疗 SARS CoV 病例。
本研究全面针对第一个已解析的 COVID-19 Mpro 结构进行了研究，并找到了适合重新用于抑制病毒 Mpro 的现有安全药物。利巴韦林、替比夫定、维生素 B12 和烟酰胺可以联合使用，用于 COVID-19 的治疗。这一举措重新定位了已经上市和批准的安全药物，以用于 COVID-19 的潜在治疗。
