Alexpandi Rajaiah, De Mesquita Joelma Freire, Pandian Shunmugiah Karutha, Ravi Arumugam Veera
Department of Biotechnology, School of Biological Sciences, Science Campus, Alagappa University, Karaikudi, India.
Laboratory of Bioinformatics and Computational Biology, Department of Genetics and Molecular Biology, Federal University of Rio de Janeiro State (UNIRIO), Rio de Janeiro, Brazil.
Front Microbiol. 2020 Jul 23;11:1796. doi: 10.3389/fmicb.2020.01796. eCollection 2020.
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 through analysis. 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.
新型冠状病毒SARS-CoV-2引发的疾病“COVID-19”在中国出现并迅速传播至其他国家；由于其在全球范围内的快速传播，世界卫生组织已将其宣布为全球紧急情况。由于尚无针对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信息促使人们通过分析寻找可能的抗SARS-CoV-2治疗方法。结果显示，喹啉、1,2,3,4-四氢-1-[(2-苯基环丙基)磺酰基]-反式-(8CI)和沙奎那韦与活性位点（半胱氨酸-组氨酸催化二元组）强烈相互作用，因此预计会阻碍SARS-CoV-2 3CLpro的活性。在113种喹啉类药物中，埃替格韦和恶喹酸能够与NTP进入通道相互作用，从而干扰SARS-CoV-2 RdRp的RNA定向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刺突糖蛋白利用人类ACE2受体进行病毒进入，靶向刺突-RBD-ACE2被视为控制感染的一种有前景的策略。结果表明，瑞拉帕迪是唯一能阻断刺突-RBD-ACE2复合物的喹啉。总之，由于喹啉、1,2,3,4-四氢-1-[(2-苯基环丙基)磺酰基]-反式-(8CI)、沙奎那韦、埃替格韦、恶喹酸和瑞拉帕迪能够靶向SARS-CoV-2的功能性大分子，且具有良好的ADMET性质，因此建议用于治疗COVID-19。
