Spatial- and Valence-Matched Neutralizing DNA Nanostructure Blocks Wild-Type SARS-CoV-2 and Omicron Variant Infection.
ACS Nano
; 16(9): 15310-15317, 2022 Sep 27.
Article
in English
| MEDLINE | ID: covidwho-2016546
ABSTRACT
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 â¼5.8 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.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Nanostructures
/
COVID-19
Topics:
Variants
Limits:
Humans
Language:
English
Journal:
ACS Nano
Year:
2022
Document Type:
Article
Similar
MEDLINE
...
LILACS
LIS