Aptamer Blocking Strategy Inhibits SARS-CoV-2 Virus Infection.

ABSTRACT: The COVID-19 pandemic caused by SARS-CoV-2 is threating global health. Inhibiting interaction of the receptor-binding domain of SARS-CoV-2 S protein (S_RBD ) and human ACE2 receptor is a promising treatment strategy. However, SARS-CoV-2 neutralizing antibodies are compromised by their risk of antibody-dependent enhancement (ADE) and unfavorably large size for intranasal delivery. To avoid these limitations, we demonstrated an aptamer blocking strategy by engineering aptamers' binding to the region on S_RBD that directly mediates ACE2 receptor engagement, leading to block SARS-CoV-2 infection. With aptamer selection against S_RBD and molecular docking, aptamer CoV2-6 was identified and applied to prevent, compete with, and substitute ACE2 from binding to S_RBD . CoV2-6 was further shortened and engineered as a circular bivalent aptamer CoV2-6C3 (cb-CoV2-6C3) to improve the stability, affinity, and inhibition efficacy. cb-CoV2-6C3 is stable in serum for more than 12 h and can be stored at room temperature for more than 14 days. Furthermore, cb-CoV2-6C3 binds to S_RBD with high affinity (K_d =0.13 nM) and blocks authentic SARS-CoV-2 virus with an IC₅₀ of 0.42 nM.

SUBMITTER: Sun M 

PROVIDER: S-EPMC8014204 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature