S Khan Lab Mardan, Khyber Pakhtunkhwa, Pakistan.
Big Data Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, P. R. China.
PLoS One. 2023 Aug 30;18(8):e0290576. doi: 10.1371/journal.pone.0290576. eCollection 2023.
Autoimmune diabetes, well-known as type 1 insulin-dependent diabetic mellitus (T1D). T1D is a prolonged condition marked by an inadequate supply of insulin. The lack is brought on by pancreatic cell death and results in hyperglycemia. The immune system, genetic predisposition, and environmental variables are just a few of the many elements that contribute significantly to the pathogenicity of T1D disease. In this study, we test flavonoids against Coxsackie virus protein to cope the type 1 diabetes. After protein target identification we perform molecular docking of flavonoids and selected target (1z8r). then performed the ADMET analysis and select the top compound the base of the docking score and the ADMET test analysis. Following that molecular dynamics simulation was performed up to 300 ns. Root means square deviation, root mean square fluctuation, secondary structure elements, and protein-ligand contacts were calculated as post-analysis of simulation. We further check the binding of the ligand with protein by performing MM-GBSA every 10 ns. Lead compound CID_5280445 was chosen as a possible medication based on analysis. The substance is non-toxic, meets the ADMET and BBB likeness requirements, and has the best interaction energy. This work will assist researchers in developing medicine and testing it as a treatment for Diabetes Mellitus Type 1 brought on by Coxsackie B4 viruses by giving them an understanding of chemicals against these viruses.
自身免疫性糖尿病，又称 1 型胰岛素依赖型糖尿病（T1D）。T1D 是一种长期存在的疾病，其特征是胰岛素供应不足。这种缺乏是由胰腺细胞死亡引起的，导致高血糖。免疫系统、遗传易感性和环境变量只是导致 T1D 疾病发病机制的众多因素中的一部分。在这项研究中，我们测试了黄酮类化合物对柯萨奇病毒蛋白的作用，以应对 1 型糖尿病。在确定蛋白质靶标后，我们对黄酮类化合物和选定的靶标（1z8r）进行了分子对接。然后进行了 ADMET 分析，并根据对接得分和 ADMET 测试分析选择了最佳化合物。之后进行了长达 300 ns 的分子动力学模拟。作为模拟后的分析，计算了均方根偏差、均方根波动、二级结构元件和蛋白质-配体接触。我们进一步通过每隔 10 ns 进行 MM-GBSA 来检查配体与蛋白质的结合情况。基于分析，选择了先导化合物 CID_5280445 作为一种可能的药物。该物质无毒性，符合 ADMET 和 BBB 相似性要求，具有最佳的相互作用能。这项工作将帮助研究人员开发药物，并通过了解针对这些病毒的化学物质，将其作为柯萨奇 B4 病毒引起的 1 型糖尿病的治疗方法进行测试。
