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Prediction of potential inhibitors for RNA-dependent RNA polymerase of SARS-CoV-2 using comprehensive drug repurposing and molecular docking approach.
International Journal of Biological Macromolecules ( IF 8.2 ) Pub Date : 2020-09-17 , DOI: 10.1016/j.ijbiomac.2020.09.098
Md Sorwer Alam Parvez 1 , Md Adnan Karim 2 , Mahmudul Hasan 3 , Jomana Jaman 4 , Ziaul Karim 5 , Tohura Tahsin 1 , Md Nazmul Hasan 6 , Mohammad Jakir Hosen 1
Affiliation  

The pandemic prevalence of COVID-19 has become a very serious global health issue. Scientists all over the world have been seriously attempting in the discovery of a drug to combat SARS-CoV-2. It has been found that RNA-dependent RNA polymerase (RdRp) plays a crucial role in SARS-CoV-2 replication, and thus could be a potential drug target. Here, comprehensive computational approaches including drug repurposing and molecular docking were employed to predict an effective drug candidate targeting RdRp of SARS-CoV-2. This study revealed that Rifabutin, Rifapentine, Fidaxomicin, 7-methyl-guanosine-5′-triphosphate-5′-guanosine and Ivermectin have a potential inhibitory interaction with RdRp of SARS-CoV-2, and could be effective drugs for COVID-19. In addition, virtual screening of the compounds from ZINC database also allowed the prediction of two compounds (ZINC09128258 and ZINC09883305) with pharmacophore features that interact effectively with RdRp of SARS-CoV-2, indicating their potentiality as effective inhibitors of the enzyme. Furthermore, ADME analysis along with analysis of toxicity was also undertaken to check the pharmacokinetics and drug-likeness properties of the two compounds. Comparative structural analysis of protein-inhibitor complexes revealed that the amino acids Y32, K47, Y122, Y129, H133, N138, D140, T141, S709 and N781 are crucial for drug surface hotspot in the RdRp of SARS-CoV-2.



中文翻译:

使用全面的药物再利用和分子对接方法预测SARS-CoV-2的RNA依赖性RNA聚合酶的潜在抑制剂。

COVID-19的大流行已经成为全球非常严重的健康问题。全世界的科学家一直在认真尝试发现一种抗击SARS-CoV-2的药物。已经发现RNA依赖性RNA聚合酶(RdRp)在SARS-CoV-2复制中起关键作用,因此可能成为潜在的药物靶标。在这里,综合的计算方法包括药物再利用和分子对接被用来预测靶向SARS-CoV-2的RdRp的有效候选药物。这项研究表明,利福布汀,利福喷丁,非达索霉素,7-甲基-鸟苷-5'-三磷酸-5'-鸟苷和伊维菌素与SARS-CoV-2的RdRp具有潜在的抑制作用,并且可能是有效治疗COVID-19的药物。此外,从ZINC数据库中对化合物进行虚拟筛选还可以预测具有药效团特征的两种化合物(ZINC09128258和ZINC09883305),这些药效团特征与SARS-CoV-2的RdRp有效相互作用,表明它们具有作为酶的有效抑制剂的潜力。此外,还进行了ADME分析和毒性分析,以检查这两种化合物的药代动力学和类药物特性。蛋白质抑制剂复合物的比较结构分析表明,氨基酸SA32-CoV-2的RdRp中的氨基酸Y32,K47,Y122,Y129,H133,N138,D138,D140,T141,S709和N781至关重要。还进行了ADME分析和毒性分析,以检查这两种化合物的药代动力学和类药物特性。蛋白质抑制剂复合物的比较结构分析表明,氨基酸SA32-CoV-2的RdRp中的氨基酸Y32,K47,Y122,Y129,H133,N138,D138,D140,T141,S709和N781至关重要。还进行了ADME分析和毒性分析,以检查这两种化合物的药代动力学和类药物特性。蛋白质抑制剂复合物的比较结构分析表明,氨基酸SA32-CoV-2的RdRp中的氨基酸Y32,K47,Y122,Y129,H133,N138,D138,D140,T141,S709和N781至关重要。

更新日期:2020-09-18
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