柯萨奇B组病毒CAR受体结合域广谱抗病毒表位与中和抗体研究

柯萨奇B组病毒（CVB）是可导致多种严重疾病的肠道病毒病原体，尚无预防疫苗或特效药物。CVB的CAR受体结合域是发现广谱抗病毒表位的理想目标。然而，目前仍缺乏对CVB与CAR相互作用精确特征的清晰认识，尚未发现CVB的CAR结合域潜在的广谱抗病毒表位的精确信息及靶向性中和抗体。课题组在前期研究中已成功初步开展了CVB与CAR受体复合物的Cryo-EM高分辨结构分析，建立了构建靶向CAR结合域的广谱中和抗体的有效策略。本研究将继续深入阐明CVB与CAR相互作用的精确特征，发现不同血清型CVB的CAR结合域的共性结构特征和关键位点，探索构建可靶向CAR结合域的广谱中和抗体，阐释其阻断病毒感染的结构基础与分子作用机制，获得CVB的CAR结合域潜在的广谱抗病毒表位的精确信息与效应抗体分子。本研究结果将有助于增进对柯萨奇病毒与受体相互作用机制的认识，为广谱疫苗和抗病毒药物研究提供理论基础和科学支持。

Coxsackievirus B (CVB) is a common enterovirus that can cause serious inflammatory diseases, for which there are currently no available vaccines or antiviral drugs. The coxsackievirus and adenovirus receptor (CAR) is a cellular receptor shared by all six serotypes of CVB, and the CAR binding domain of CVB is a potential broad-spectrum antiviral target. However, the structural characteristics of CVB-CAR interaction are not well understood, and no broadly neutralizing anti-CVB antibody targeting the CAR binding domain has been found. Previously, we obtained the near-atomic-resolution cryo-electron microscopy (Cryo-EM) reconstruction of CVB-CAR complex and established an effective strategy for screening broadly neutralizing antibodies targeting the CVB-CAR binding domain. In this study, we will further analyze the characteristics of CVB-CAR interactions, and identify common structural features and key amino acid residues in CAR-binding domains of different CVB serotypes as broad-spectrum antiviral candidate targets. Moreover, we will explore the construction of broadly neutralizing anti-CVB antibodies targeting the CAR binding domain, and clarify the structural and molecular mechanisms underlying antibody-mediated cross-neutralization. We expect the results of this study will improve our understanding of the coxsackievirus-receptor interactions, and provide theoretical basis and scientific support for the development of novel vaccines or antiviral drugs.