基于等离激元材料的新冠病毒变异检测与免疫结合分析

病毒变异是影响其传染性、致病性、抗药性和免疫逃逸的根本原因。快速确定病毒种类及其突变情况，进行病毒突变对其与宿主受体蛋白结合影响的分析，对于疫情防控及临床诊断和治疗具有重要意义。课题组前期基于等离激元材料构建了高通量核酸/蛋白质多重检测平台，其中核酸检测灵敏度达单拷贝，能够实现单碱基区分，蛋白质检测灵敏度达飞摩级。本课题以等离激元核酸检测平台为基础开展了新冠病毒变异株即时检测(Point-of-care Testing，POCT)的可行性验证，并完成在新冠病毒(SARS-CoV-2)检测中的临床实验验证，实现了100%的检测特异性。同时，以等离激元蛋白质检测平台为基础，结合蛋白质建模和分子动力学模拟技术，构建了一套评价体系以计算多肽与蛋白的结合自由能，进而评价其结合强度，从多肽层面探究了SARS-CoV-2的受体结构域(Receptor-Binding Domain，RBD)突变对其与人血管紧张素转换酶2(Angiotensin-converting enzyme 2，ACE2)蛋白结合的影响。通过计算不同RBD的子序列多肽与ACE2的结合强度，发现多肽YNYLYRLFRKSNLKP与ACE2的结合强度显著高于其他多肽，在RBD靶向ACE2中具有潜在的重要意义。通过在等离激元荧光增强材料表面构建多肽微阵列并表征其与ACE2蛋白的结合强度，验证了这一体系的预测准确率达80%。本课题有望为未来病原体的快速检测及突变区分以及多肽药物或疫苗的筛选提供新的思路。

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