Thurakkal Liya, Singh Satyam, Roy Rajarshi, Kar Parimal, Sadhukhan Sushabhan, Porel Mintu
Discipline of Chemistry, Indian Institute of Technology Palakkad, Kerala 678 557, India.
Discipline of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Madhya Pradesh 453 552, India.
Chem Phys Lett. 2021 Jan 16;763:138193. doi: 10.1016/j.cplett.2020.138193. Epub 2020 Nov 15.
The emerging paradigm shift from 'one molecule, one target, for one disease' towards 'multi-targeted small molecules' has paved an ingenious pathway in drug discovery in recent years. We extracted this idea for the investigation of drugs for COVID-19. Perceiving the importance of organosulfur compounds, seventy-six known organosulfur compounds were screened and studied for the interaction with multiple SARS-CoV-2 target proteins by molecular dynamics simulation. Lurasidone and its derivatives displayed substantial binding affinity against five proteins (Mpro, PLpro, Spro, helicase and RdRp). The pharmacokinetics, ADMET properties and target prediction studies performed in this work further potentiates the effectiveness against SARS-CoV-2.
近年来，从“一种分子，一个靶点，针对一种疾病”到“多靶点小分子”的新兴范式转变为药物发现开辟了一条巧妙的途径。我们提取了这一理念用于研究治疗新冠肺炎的药物。鉴于有机硫化合物的重要性，通过分子动力学模拟筛选并研究了76种已知的有机硫化合物与多种新冠病毒靶点蛋白的相互作用。鲁拉西酮及其衍生物对五种蛋白质（Mpro、PLpro、Spro、解旋酶和RdRp）表现出显著的结合亲和力。这项工作中进行的药代动力学、ADMET性质和靶点预测研究进一步增强了对新冠病毒的有效性。
