Amin Amina, Rasheed Muhammad A, Diwan Rana A, Shahid Muhammad, Bano Saddia, Riaz Adnan, Iqbal Muhammad N, Sajid Muhammad W
Department of Biosciences, COMSATS University Islamabad, Sahiwal Campus, Sahiwal, Pakistan.
Department of Community Medicine, Sahiwal Medical College, Sahiwal, Pakistan.
Curr Comput Aided Drug Des. 2020;16(3):318-326. doi: 10.2174/1573409915666190820154422.
Insulin-dependent Diabetes Mellitus Type 1 (T1D) also referred to as autoimmune diabetes. T1D is a chronic disease which is characterized by way of insulin deficiency. The deficiency is due to the loss of pancreatic β cells and leads to hyperglycemia. There are many factors which play a significant role in T1D disease pathogenicity including genetic predisposition, the immune system, and environmental factors. The environmental factors may include Coxsackie B4 virus, a small RNA virus.
The objective of current in silico study is to identify active lead compounds against Coxsackie B4 virus, a small RNA virus which has been reported in diabetic patients after PCR. There is a need to predict inhibitors against TID caused by Coxsackie B4 viral protein that may be used as a drug against TID in the future.
For this purpose, different bioinformatics databases and tools were used. The protein structure generation and validation, retrieval of ligands and their properties analysis were performed by different databases, web servers, and software tools. Moreover, the docking tools were used to identify the target site of the protein and interaction of different inhibitors with the target protein molecule.
Based on the analysis, two lead compounds ZINC00034488 and ZINC00034585 were selected as potential drugs. These compounds are non-toxic and have best interaction energy and fulfill Lipinski rule, Veber rule, Ghose Rule, Weighted QED, Unweighted QED and BBB likeness parameters.
Our work will help researchers to get an idea about the understanding of chemicals against Coxsackie B4 Viruses and helpful to design a drug and test these chemicals to overcome Diabetes Mellitus Type 1 caused by Coxsackie B4 virus.
1型胰岛素依赖型糖尿病（T1D）也被称为自身免疫性糖尿病。T1D是一种以胰岛素缺乏为特征的慢性疾病。这种缺乏是由于胰腺β细胞的丧失导致高血糖。有许多因素在T1D疾病的发病机制中起重要作用，包括遗传易感性、免疫系统和环境因素。环境因素可能包括柯萨奇B4病毒，一种小RNA病毒。
当前计算机模拟研究的目的是识别针对柯萨奇B4病毒的活性先导化合物，柯萨奇B4病毒是一种小RNA病毒，在糖尿病患者的PCR检测后被报道。有必要预测由柯萨奇B4病毒蛋白引起的TID的抑制剂，这些抑制剂未来可能用作治疗TID的药物。
为此，使用了不同的生物信息学数据库和工具。通过不同的数据库、网络服务器和软件工具进行蛋白质结构生成和验证、配体检索及其性质分析。此外，对接工具用于识别蛋白质的靶位点以及不同抑制剂与靶蛋白分子的相互作用。
基于分析，选择了两种先导化合物ZINC00034488和ZINC00034585作为潜在药物。这些化合物无毒，具有最佳的相互作用能，符合Lipinski规则、Veber规则、Ghose规则、加权QED、未加权QED和血脑屏障相似性参数。
我们的工作将有助于研究人员了解针对柯萨奇B4病毒的化学物质，并有助于设计药物并测试这些化学物质以克服由柯萨奇B4病毒引起的1型糖尿病。
