关注B.1.617和NSP12突变体对SARS-Cov-2变体的分子对接和模拟研究

IF 1.2 Q3 MULTIDISCIPLINARY SCIENCES
Vinuthna Vani Madishetti, Sudhakar Reddy, S. Kalagara, Ashish Garg, Sreenivas Enaganti, Sardar Hussain
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引用次数: 0

摘要

摘要人类冠状病毒(HCoV),包括严重急性呼吸综合征冠状病毒(SARS-CoV)和2019年新型冠状病毒(2019-nCoV)(也称为SARS-CoV-2),已导致全球高发病率和高死亡率流行病。正在积极研究寻找对抗2019-nCoV/SARS-CoV-2的有效药物。电子筛查是识别命中率的最佳方法,与从头发现药物相比,可以缩短时间并降低成本。最近,CoV2突变在印度引起了很大的关注,特别是在非结构蛋白(NSPs)和刺突蛋白(B.1.617)上,它们是在介导病毒复制和转录中发挥关键作用的关键靶点。在此,本研究分析了严重急性呼吸系统综合征冠状病毒2型变异株的NSPs和刺突的结构方面。从蛋白质数据库中检索或建模NSPs和S刺突蛋白的三维结构。我们的研究使用了一个抗病毒化合物库的数据集,该库包含49万个类药物配体和结构多样的生物活性支架。最初,对文库化合物与参考药物分子进行分子比对,以找到与场点匹配的靶标。相似性得分大于0.6的抗病毒化合物;被选择用于与野生和突变NSP以及严重急性呼吸系统综合征冠状病毒2变种B.1.617的S刺突蛋白进行进一步对接研究。对接研究确定了一种有效的类似物MA-11,它对野生和突变蛋白表现出最高的结合亲和力。此外,对所选化合物的分子动力学模拟研究证实了它们与NSP12和刺突活性位点的完美匹配,并为进一步的先导优化和合理的药物设计提供了方向。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Insilico Screening for Identification of Hits against SARS-Cov-2 Variant of Concern B.1.617 and NSP12 Mutants by Molecular Docking and Simulation Studies
Abstract Human coronaviruses (HCoVs), including severe acute respiratory syndrome coronavirus (SARS-CoV) and 2019 novel coronavirus (2019-nCoV), also known as SARS-CoV-2, have caused global epidemics with high morbidity and mortality. Active research on finding effective drugs against 2019-nCoV/SARS-CoV-2 is going on. In silico screening represents the best approach for hits identification and could shorten the time and reduce cost compared to de novo drug discovery. Recently, CoV2 mutations have been a big concern in India, particularly on non-structural proteins (NSPs) and Spike Protein (B.1.617) which are the key targets that play a pivotal role in mediating viral replication and transcription. Herein, this study analyzed the NSPs and spike’s structural aspects of mutant strains of SARS-CoV-2. The three-dimensional structures of NSPs and S Spike proteins were retrieved from the protein data bank or modeled. And a dataset of an antiviral compound library containing 490,000 drug-like ligands and structurally diverse biologically active scaffolds was used for our studies. Initially, the molecular alignment was performed for library compounds with the reference drug molecule to find targets that match the field points. Antiviral compounds having a similarity score >0.6; were selected for further docking studies with wild and mutant NSPs and S Spike protein of SARS-CoV-2 variant B.1.617. The docking studies identified a potent analog MA-11, which exhibited the highest binding affinity towards wild and mutant proteins. Further, molecular dynamics simulation studies of selected compounds confirmed their perfect fitting into NSP12 and spike active sites and offer direction for further lead optimization and rational drug design.
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来源期刊
The EuroBiotech Journal
The EuroBiotech Journal Agricultural and Biological Sciences-Food Science
CiteScore
3.60
自引率
0.00%
发文量
17
审稿时长
10 weeks
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