Journal
ACS NANO
Volume -, Issue -, Pages -Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.2c06803
Keywords
spatial-patterned interaction; DNA nanotechnology; neutralizing aptamer; SARS-CoV-2 neutralization; Omicron
Categories
Funding
- National Natural Science Foundation of China [22022409, 21735004, 21874089, 21775128]
- Program for Changjiang Scholars and Innovative Research Team in University [IRT13036]
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Researchers have successfully achieved neutralization of SARS-CoV-2 by designing a DNA framework-guided trimer of neutralizing aptamers. The design utilizes the precise spatial organization of the DNA framework to enhance the interaction between the aptamers and the spike protein of the virus, effectively preventing viral infection through the formation of a nanoscale barrier.
Natural ligand-receptor interactions that play pivotal roles in biological events are ideal models for design and assembly of artificial recognition molecules. Herein, aiming at the structural characteristics of the spike trimer and infection mechanism of SARS-CoV-2, we have designed a DNA framework-guided spatial-patterned neutralizing aptamer trimer for SARS-CoV-2 neutralization. The & SIM;5.8 nm tetrahedral DNA framework affords precise spatial organization and matched valence as four neutralizing aptamers (MATCH-4), which matches with nanometer precision the topmost surface of SARS-CoV-2 spike trimer, enhancing the interaction between MATCH-4 and spike trimer. Moreover, the DNA framework provides a dimensionally complementary nanoscale barrier to prevent the spike trimer-ACE2 interaction and the conformational transition, thereby inhibiting SARS-CoV-2-host cell fusion and infection. As a result, the spatial-and valence-matched MATCH-4 ensures improved binding affinity and neutralizing activity against SARS-CoV-2 and its varied mutant strains, particularly the current Omicron variant, that are evasive of the majority of existing neutralizing antibodies. In addition, because neutralizing aptamers specific to other targets can be evolved and assembled, the present design has the potential to inhibit other wide-range and emerging pathogens.
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