奥司他韦是一线抗病毒药物,尤其是在基层医院。在2019年冠状病毒病(COVID-19)持续爆发期间,大多数有症状的COVID-19患者使用了奥司他韦.考虑到它作为抗病毒药物的流行和重要作用,有必要评估奥司他韦在COVID-19治疗中的作用。
评价奥司他韦抗COVID-19的作用。
Swiss模型用于构建核蛋白(NC)的N端RNA结合域(NRBD)的结构,木瓜蛋白酶(PLpro),和严重急性呼吸综合征冠状病毒2(SARS-CoV-2)的RNA定向RNA聚合酶(RdRp)。进行TM-align程序以将病毒蛋白的结构与流感A的神经氨酸酶的结构进行比较。分子对接用于分析奥司他韦与病毒蛋白的活性中心有效结合的理论可能性。体外研究用于评估奥司他韦对SARS-CoV-2的抗病毒效率。通过临床病例分析,我们对奥司他韦使用史是否影响疾病进展进行了统计学评估.
NRBD的结构,PLpro,RdRp构建成功。TM-align的结果表明,S蛋白,NRBD,3C样蛋白酶(3CLpro),PLPro,RdRp在结构上与甲型神经氨酸酶相似,TM评分分别为0.30077、0.19254、0.28766、0.30666和0.34047。有趣的是,通过分子对接分析,发现3CLpro的活性中心与甲型流感神经氨酸酶的活性中心相似,我们发现奥司他韦羧酸更有利于与3CLpro的活性位点有效结合,但与阳性组相比,其抑制作用不强。最后,我们使用体外研究和回顾性病例分析来验证我们的推测.我们发现奥司他韦对SARS-CoV-2的体外研究无效,奥司他韦的临床使用并没有改善患者的症状和体征,也没有减缓疾病的进展。
我们认为奥司他韦不适合治疗COVID-19。在新型冠状病毒爆发期间,当奥司他韦服用后对患者无效时,卫生工作者应高度警惕COVID-19的可能性。
Oseltamivir is a first-line antiviral drug, especially in primary hospitals. During the ongoing outbreak of coronavirus disease 2019 (COVID-19), most patients with COVID-19 who are symptomatic have used oseltamivir. Considering its popular and important role as an antiviral drug, it is necessary to evaluate oseltamivir in the treatment of COVID-19.
To evaluate the effect of oseltamivir against COVID-19.
Swiss-model was used to construct the structure of the N-terminal RNA-binding domain (NRBD) of the nucleoprotein (NC), papain-like protease (PLpro), and RNA-directed RNA polymerase (RdRp) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). TM-align program was performed to compare the structure of the viral proteins with the structure of the neuraminidase of influenza A. Molecular docking was used to analyze the theoretical possibility of effective binding of oseltamivir with the active centers of the viral proteins. In vitro
study was used to evaluate the antiviral efficiency of oseltamivir against SARS-CoV-2. By clinical case analysis, we statistically evaluated whether the history of oseltamivir use influenced the progression of the disease.
The structures of NRBD, PLpro, and RdRp were built successfully. The results from TM-align suggested that the S protein, NRBD, 3C-like protease (3CLpro), PLPrO, and RdRp were structurally similar to the influenza A neuraminidase, with TM-scores of 0.30077, 0.19254, 0.28766, 0.30666, and 0.34047, respectively. Interestingly, the active center of 3CL pro was found to be similar to the active center from the neuraminidase of influenza A. Through an analysis of molecular docking, we discovered that oseltamivir carboxylic acid was more favorable to bind to the active site of 3CLpro effectively, but its inhibitory effect was not strong compared with the positive group. Finally, we used in vitro
study and retrospective case analysis to verify our speculations. We found that oseltamivir is ineffective against SARS-CoV-2 in vitro
study and the clinical use of oseltamivir did not improve the patients\' symptoms and signs and did not slow the disease progression.
We consider that oseltamivir isn\'t suitable for the treatment of COVID-19. During the outbreak of novel coronavirus, when oseltamivir is not effective for the patients after they take it, health workers should be highly vigilant about the possibility of COVID-19.