4.8 Article

Spherical neutralizing aptamer suppresses SARS-CoV-2 Omicron escape

Journal

NANO TODAY
Volume 44, Issue -, Pages -

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.nantod.2022.101499

Keywords

SARS-CoV-2 Omicron; Aptamer; Neutralization; Spherical nucleic acids

Funding

  1. National Natural Science Foundation of China [22022409, 21735004, 21874089]
  2. Program for Changjiang Scholars and Innovative Research Teams in University [IRT13036]
  3. National Science Fund for Fostering Talents in Basic Science (NFFTBS) [J1310024]
  4. XMU Training Program of Innovation and Entrepreneurship for Undergraduates

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The Omicron variant of SARS-CoV-2 has been spreading rapidly worldwide. It has been found to evade the human immune response. In this study, a new approach was used to block the interaction between the Omicron variant and host cells, effectively inhibiting its infection.
Recently, the SARS-CoV-2 Omicron has spread very quickly worldwide. Several studies have indicated that the Omicron variant causes a substantial evasion of the humoral immune response and the majority of existing SARS-CoV-2 neutralizing antibodies. Here we address this challenge by applying a spherical cocktail neutralizing aptamer-gold nanoparticle (SNAP) to block the interaction of Omicron receptor binding domain (RBD) and host Angiotensin-Converting Enzyme 2 (ACE2). With the synergetic blocking strategy based on multivalent multisite aptamer binding and steric hindrance by the size-matched gold scaffold, the SNAP conjugate tightly binds to Omicron RBD with a dissociation constant of 13.6 pM, almost completely blocking the infection of Omicron pseudovirus with a half-maximal inhibitory concentration of 35.9 pM. Overall, the SNAP strategy not only fills the gap of the humoral immune evasion caused by clustered mutations on Omicron, but also provides a clue for the development of new broad neutralizing reagents against future variants. (C) 2022 Elsevier Ltd. All rights reserved.

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