Spherical Neutralizing Aptamer Inhibits SARS-CoV-2 Infection
2021
New neutralizing agents against SARS-CoV-2 and the associated
mutant strains are urgently needed for the treatment and prophylaxis of COVID-19.
Herein, we develop a spherical cocktail neutralizing aptamer-gold
nanoparticle (SNAP) to synergistically block the interaction of SARS-CoV-2
receptor-binding domain (RBD) and angiotensin-converting enzyme-2 (ACE2). Taking
advantage of the simultaneous recognition of multi-homologous and multi-heterogenous
neutralizing aptamers and dimensionally matched nano-scaffolds, the SNAP
exhibits increased affinity to the RBD with a dissociation constant value of 5.46
pM and potent neutralization against authentic SARS-CoV-2 with a half-maximal
inhibitory concentration of 142.80 aM. Additional benefits include the multi-epitope
blocking capability of the aptamer cocktail and the steric hindrance of the
nano-scaffold, which further covers the ACE2 binding interfaces and affects the
conformational transition of the spike protein. As a result, the SNAP strategy exhibits
broad neutralizing activity, almost completely blocking the infection of N501Y and D614G mutant strains. Overall, the SNAP
strategy provides a new direction for development of anti-virus infection
mechanisms, both to fight the COVID-19 pandemic and serve as a powerful
technical reserve for future unknown pandemics.
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