Quinolines-Based SARS-CoV-2 3CLpro and RdRp Inhibitors and Spike-RBD-ACE2 Inhibitor for Drug-Repurposing Against COVID-19: Anin silicoAnalysis
Quinolines-Based SARS-CoV-2 3CLpro and RdRp Inhibitors and Spike-RBD-ACE2 Inhibitor for Drug-Repurposing Against COVID-19: Anin silicoAnalysis
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DOI：
10.3389/fmicb.2020.01796
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发表时间：
2020-07-23
影响因子：
5.2
通讯作者：
Ravi, Arumugam Veera
中科院分区：
文献类型：
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作者：
Alexpandi, Rajaiah;De Mesquita, Joelma Freire;Ravi, Arumugam Veera
新型冠状病毒SARS-CoV-2疾病“COVID-19”在中国出现并迅速蔓延到其他国家;由于其在全球范围内的快速传播，世界卫生组织已宣布其为全球紧急情况。由于没有治疗COVID-19的特定治疗方法，因此在现有药物中寻找合适的治疗方法似乎很有价值。冠状病毒大分子的结构可用性鼓励了通过计算机分析发现可能的抗SARS-CoV-2疗法。结果表明，喹啉、1，2，3，4-四氢-1-[（2-苯基环丙基）磺酰基]-反式-（8 CI）和沙奎那韦与SARS-CoV-2 3CLpro的活性位点（Cys-His催化二联体）有较强的相互作用，从而可能阻碍SARS-CoV-2 3CLpro的活性。在113种喹啉类药物中，elvitegravir和oxolinic acid能够与NTP进入通道相互作用，从而干扰SARS-CoV-2 RdRp的RNA指导的5 '-3 '聚合酶活性。生物活性预测结果也验证了对接研究的结果。此外，由于SARS-CoV-2 Spike-glycoprotein使用人ACE 2受体用于病毒进入，靶向Spike-RBD-ACE 2已被视为控制感染的有希望的策略。结果表明，rilapradib是唯一可以中断Spike-RBD-ACE 2复合物的喹啉。总之，由于它们能够靶向SARS-CoV-2的功能性大分子，沿着具有积极的ADMET性质，喹啉、1，2，3，4-四氢-1-[（2-苯基环丙基）磺酰基]-反式-（8 CI）、沙奎那韦、埃替拉韦、奥喹啉酸和利拉拉迪被建议用于治疗COVID-19。
The novel coronavirus SARS-CoV-2 disease "COVID-19" emerged in China and rapidly spread to other countries; due to its rapid worldwide spread, the WHO has declared this as a global emergency. As there is no specific treatment prescribed to treat COVID-19, the seeking of suitable therapeutics among existing drugs seems valuable. The structure availability of coronavirus macromolecules has encouraged the finding of conceivable anti-SARS-CoV-2 therapeutics throughin silicoanalysis. The results reveal that quinoline,1,2,3,4-tetrahydro-1-[(2-phenylcyclopropyl)sulfonyl]-trans-(8CI) and saquinavir strongly interact with the active site (Cys-His catalytic dyad), thereby are predicted to hinder the activity of SARS-CoV-2 3CLpro. Out of 113 quinoline-drugs, elvitegravir and oxolinic acid are able to interact with the NTP entry-channel and thus interfere with the RNA-directed 5 '-3 ' polymerase activity of SARS-CoV-2 RdRp. The bioactivity-prediction results also validate the outcome of the docking study. Moreover, as SARS-CoV-2 Spike-glycoprotein uses human ACE2-receptor for viral entry, targeting the Spike-RBD-ACE2 has been viewed as a promising strategy to control the infection. The result shows rilapladib is the only quinoline that can interrupt the Spike-RBD-ACE2 complex. In conclusion, owing to their ability to target functional macromolecules of SARS-CoV-2, along with positive ADMET properties, quinoline,1,2,3,4-tetrahydro-1-[(2-phenylcyclopropyl)sulfonyl]-trans-(8CI), saquinavir, elvitegravir, oxolinic acid, and rilapladib are suggested for the treatment of COVID-19.