新型SARS-Cov-2刺突受体结合域潜在抑制的抗病毒药物和天然化合物的虚拟筛选

Shilu M. Mathew, F. Benslimane, A. Althani, H. Yassine
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引用次数: 1

摘要

背景:SARS-CoV-2的刺突(S)蛋白含有介导病毒进入宿主细胞的受体结合域(RBD)。本研究的目的是通过对化学和天然化合物的计算筛选来鉴定针对s蛋白RBD结构域的新型抑制剂。方法:根据最近分离的SARS-CoV蛋白结构和先前描述的SARS-CoV蛋白结构建立S蛋白模型。使用CLC Drug Discovery计算筛选现有处方药物(n= 22)、抗病毒天然药物(n=100)、天然化合物(n= 35032)的潜在抑制作用。同时进行QSAR。结果:在目前处方的治疗SARS-CoV2的药物中,羟氯喹和favipiravir是最佳的结合剂,平均为4h键,结合亲和力(BA)为-36.66 kcal·mol−1,相互作用能(IE)为-6.63 kcal·mol−1。经抗病毒化合物评价,fosamprenavir和abacavir均能有效结合5h键,平均BA为-18.75 kcal·mol−1,IE为-3.57 kcal·mol−1。此外,筛选了100种天然抗病毒化合物,预测了甘草酸苷、nepritin、punicalagin、EGCG和茶黄素的潜在结合模式(平均BA: -49.88 kcal·mol−1,IE: -4.35 kcal·mol−1)。此外,该研究还报道了25种天然化合物的有效结合,其平均BA提高了51.46 kcal·mol−1。结论:通过计算筛选,我们确定了与RBD区域结合的潜在SARSCoV-2刺突抑制剂。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Virtual Screening of Anti-Viral Drugs and Natural Compounds for Potential Inhibition of the Novel SARS-Cov-2 Spike Receptor-Binding Domain
Background: The spike (S) protein of SARS-CoV-2 harbors the receptor-binding domain (RBD) that mediates the virus's entry to host cells. The aim of this study was to identify novel inhibitors that target the RBD domain of S-protein through computational screening of chemical and natural compounds. Method: The S protein was modelled from the recently resolved and the previously described SARS-CoV protein structures. CLC Drug Discovery was used to computationally screen for potential inhibitory effects of currently prescribed drugs (n= 22) anti-viral natural drugs (n=100), natural compounds (n= 35032). QSAR was also performed. Results: Among currently precribed drugs to treat SARS-CoV2, hydroxychloroquine and favipiravir were identified as the best binders with an average of 4Hbonds, the binding affinity (BA): -36.66 kcal·mol−1, and interaction energy (IE): -6.63 kcal·mol−1. After the evaluation of anti-viral compounds, fosamprenavir and abacavir showed effective binding of 5H-bonds, with average BA: -18.75 kcal·mol−1, and IE: -3.57 kcal·mol−1. Furthermore, screening of 100 natural anti-viral compounds predicted potential binding modes of glycyrrhizin, nepritin, punicalagin, EGCG, and theaflavin (average BA: -49.88 kcal·mol−1, and IE: -4.35 kcal·mol−1). Additionally, the study reports 25 natural compounds that showed effective binding with an improved average BA: 51.46 kcal·mol−1. Conclusion: Using computational screening, we identified potential SARSCoV-2 spike inhibitors that bind to the RBD region.
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