The MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, the Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.
Institute of Molecular Medicine and Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, State Key Laboratory of Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
J Am Chem Soc. 2022 Jul 27;144(29):13146-13153. doi: 10.1021/jacs.2c02764. Epub 2022 Jun 30.
Broad-spectrum anti-SARS-CoV-2 strategies that can inhibit the infection of wild-type and mutant strains would alleviate their threats to global public health. Here, we propose an icosahedral DNA framework for the assembly of up to 30 spatially arranged neutralizing aptamers (IDNA-30) to inhibit viral infection. Each triangular plane of IDNA-30 is composed of three precisely positioned aptamers topologically matching the SARS-CoV-2 spike trimer, thus forming a multivalent spatially patterned binding. Due to its multiple binding sites and moderate size, multifaced IDNA-30 induces aggregation of viruses. The rigid icosahedron framework afforded by four helixes not only forms a steric barrier to prevent the virus from binding to the host but also limits the conformational transformation of the SARS-CoV-2 spike trimer. Combining multivalent topologically patterned aptamers with structurally well-defined nanoformulations, IDNA-30 exhibits excellent broad-spectrum neutralization against SARS-CoV-2, including almost completely blocking the infection of Omicron pseudovirus. Overall, this multidimensional neutralizing strategy provides a new direction for the assembly of neutralizing reagents to enhance their inhibitory effect against SARS-CoV-2 infection and combat other disease-causing viruses.
广谱抗 SARS-CoV-2 策略可以抑制野生型和突变株的感染，从而减轻它们对全球公共卫生的威胁。在这里，我们提出了一种二十面体 DNA 框架，用于组装多达 30 个空间排列的中和适体（IDNA-30）以抑制病毒感染。IDNA-30 的每个三角面由三个拓扑上与 SARS-CoV-2 刺突三聚体匹配的精确定位适体组成，从而形成多价空间图案结合。由于其多个结合位点和适中的大小，多面 IDNA-30 诱导病毒聚集。由四条螺旋形成的刚性二十面体框架不仅形成了阻止病毒与宿主结合的空间障碍，而且限制了 SARS-CoV-2 刺突三聚体的构象转变。将多价拓扑图案适体与结构明确的纳米制剂结合使用，IDNA-30 对 SARS-CoV-2 表现出优异的广谱中和作用，包括几乎完全阻断奥密克戎假病毒的感染。总的来说，这种多维中和策略为组装中和试剂提供了一个新的方向，以增强它们对 SARS-CoV-2 感染的抑制作用，并对抗其他致病病毒。
