Abstract：
Multiple sclerosis (MS), an intricate neurological disorder, continues to challenge our understanding of the pivotal interplay between the immune system and the central nervous system (CNS). This condition arises from the immune system\'s misdirected attack on nerve fiber protection, known as myelin sheath, alongside nerve fibers themselves. This enigmatic condition, characterized by demyelination and varied clinical manifestations, prompts exploration into its multifaceted etiology and potential therapeutic avenues. Research has revealed a potential connection between Epstein Barr virus (EBV), specifically Epstein Barr Nuclear Antigen 1 (EBNA-1), and MS. The immune response to EBNA-1 antigen triggers the production of anti-EBNA-1 molecules, including IgG that identify a similar amino acid sequence to EBNA-1 in myelin, inadvertently targeting myelin sheath and contributing to MS progression. Currently, no treatment exists for EBNA-1-induced MS apart from symptom management. Addressing this, a novel potential therapeutic avenue utilizing small interference RNAs (siRNA) has been designed. By targeting the conserved EBNA-1 gene sequences in EBV types 1 and 2, five potential siRNAs were identified in our analysis. Thorough evaluations encompassing off-target binding, thermodynamics and secondary structure elucidation, efficacy prediction, siRNA-mRNA sequence binding affinity exploration, melting temperature, and docking of siRNAs with human argonaute protein 2 (AGO2) were conducted to elucidate the siRNAs efficiency. These designed siRNA molecules harnessed promising silencing activity in the EBNA-1 gene encoding the EBNA-1 antigen protein and thus have the potential to mitigate the severity of this dangerous virus.
摘要：
多发性硬化症（MS），复杂的神经紊乱,继续挑战我们对免疫系统和中枢神经系统（CNS）之间关键相互作用的理解。这种情况源于免疫系统对神经纤维保护的误导攻击，被称为髓鞘，除了神经纤维本身。这个神秘的条件，以脱髓鞘和各种临床表现为特征，提示探索其多方面的病因和潜在的治疗途径。研究揭示了爱泼斯坦巴尔病毒（EBV）之间的潜在联系，特别是爱泼斯坦巴尔核抗原1（EBNA-1），和女士对EBNA-1抗原的免疫反应触发了抗EBNA-1分子的产生，包括识别髓鞘中与EBNA-1相似的氨基酸序列的IgG，无意中靶向髓鞘并导致MS进展。目前,对于EBNA-1诱导的MS,除症状管理外,尚无治疗方法。解决这个问题，已经设计了一种利用小干扰RNA(siRNA)的新的潜在治疗途径.通过靶向1型和2型EBV中保守的EBNA-1基因序列,在我们的分析中鉴定了5种潜在的siRNA。包括脱靶结合的彻底评估，热力学和二级结构阐明，疗效预测，siRNA-mRNA序列结合亲和力探索，熔化温度,并进行siRNA与人argonaute蛋白2（AGO2）的对接以阐明siRNA的效率。这些设计的siRNA分子在编码EBNA-1抗原蛋白的EBNA-1基因中利用了有希望的沉默活性，因此具有减轻这种危险病毒严重程度的潜力。
