Design of novel pyrimidine based remdesivir analogues with dual target specificity for SARS CoV-2: A computational approach.
International journal of biological macromolecules(2023)
摘要
As the world undergone unpreceded time of tragedy with the corona virus, many researchers have raised to showcase their scientific contributions in terms of novel configured anti-viral drugs until now. Herein, we designed pyrimidine based nucleotides and assessed for the binding capability with SARS-CoV-2 viral replication targets of nsp12 RNA-dependent RNA polymerase and Mpro main protease. Molecular docking studies showed all the designed compounds to possess good binding affinity, with a few compounds which outperforms the control drug remdesivir GS-5743 and its active form GS-441524. Further molecular dynamics simulation studies confirmed their stability and preservation of the non-covalent interactions. Based on the present findings Ligand2-BzV_0Tyr, ligand3-BzV_0Ura, and ligand5-EeV_0Tyr showed good binding affinity with Mpro, whereas, ligand1-BzV_0Cys and Ligand2-BzV_0Tyr showed good binding affinity with RdRp, thus could act as potential lead compounds against SARS-CoV-2, which needs further validation studies. In particular, Ligand2-BzV_0Tyr could be more beneficial candidate with the dual target specificity for Mpro and RdRp.
更多查看译文
关键词
SARS CoV-2,Pyrimidine based remdesivir analogues,Corona virus,Molecular modelling,COVID-19,Main protease,RNA -dependent DNA polymerase,Molecular dynamics simulations,Covalent docking
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要