School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China.
Lab of Toxicology and Pharmacology, Faculty of Naval Medicine, Naval Medical University, Shanghai 200433, China.
Molecules. 2023 Sep 28;28(19):6838. doi: 10.3390/molecules28196838.
Mpox virus (MPXV), the most pathogenic zoonotic orthopoxvirus, caused worldwide concern during the SARS-CoV-2 epidemic. Growing evidence suggests that the MPXV surface protein A29 could be a specific diagnostic marker for immunological detection. In this study, a fully synthetic phage display library was screened, revealing two nanobodies (A1 and H8) that specifically recognize A29. Subsequently, an in vitro affinity maturation strategy based on computer-aided design was proposed by building and docking the A29 and A1 three-dimensional structures. Ligand-receptor binding and molecular dynamics simulations were performed to predict binding modes and key residues. Three mutant antibodies were predicted using the platform, increasing the affinity by approximately 10-fold compared with the parental form. These results will facilitate the application of computers in antibody optimization and reduce the cost of antibody development; moreover, the predicted antibodies provide a reference for establishing an immunological response against MPXV.
猴痘病毒（MPXV）是最具致病性的正痘病毒属动物源性病毒，在 SARS-CoV-2 流行期间引起了全球关注。越来越多的证据表明，MPXV 表面蛋白 A29 可能是免疫检测的特异性诊断标记物。本研究通过筛选全合成噬菌体展示文库，发现了两种能够特异性识别 A29 的纳米抗体（A1 和 H8）。随后，通过构建和对接 A29 和 A1 的三维结构，提出了一种基于计算机辅助设计的体外亲和力成熟策略。进行配体-受体结合和分子动力学模拟，以预测结合模式和关键残基。利用该平台预测了 3 种突变抗体，与亲本形式相比，其亲和力增加了约 10 倍。这些结果将促进计算机在抗体优化中的应用，并降低抗体开发的成本；此外，预测的抗体为建立针对 MPXV 的免疫反应提供了参考。
