Spatially patterned neutralizing icosahedral DNA nanocage for efficient SARS-CoV-2 blocking

New neutralizing strategies against SARS-CoV-2 and associated variants are urgently needed for the treatment of COVID-19. Targeting the SARS-CoV-2 multi-spike trimers, an icosahedral DNA framework was assembled to spatially arrange up to thirty neutralizing aptamers (IDNA-30) with nanometer precision to inhibit viral infection. Each triangular plane of IDNA-30 is composed of three precisely positioned aptamers topologically matching SARS-CoV-2 spike trimer, thus forming a multivalent spatially patterned binding. Additionally, due to its multiple binding sites and moderate size, multifaced IDNA induces aggregation of viruses. Moreover, the rigid icosahedron framework afforded by four-helixes not only forms a steric barrier to prevent the virus from binding to host, but also limits the conformational transformation of SARS-CoV-2 spike trimer. Combining multivalent topologically patterned aptamers with structurally well-defined nano-formulations, IDNA-30 exhibits excellent neutralization against SARS-CoV-2 and a broad neutralizing activity against several mutant strains. Overall, this spatially matched neutralizing strategy provides a new direction for the assembly of neutralizing reagents to enhance the inhibitory effect of SARS-CoV-2 infection and combat other disease-causing viruses.