Identification of Pan‐Coronavirus Neutralizing Aptamers Through CRISmers Targeting the Conserved Fusion Peptide

A series of coronavirus outbreaks emphasize the necessity to develop pan-coronavirus therapeutics. Previously, the CRISmers system is developed, a Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated proteins (CRISPR/Cas)-mediated cellular screening platform for the identification of RNA aptamers. In this study, CRISmers are applied to target the fusion peptide (FP) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a conserved region across coronavirus genera, with E.coli serving as the screening host. From this approach, a lead aptamer, #FP-10 is identified, which demonstrates potent pan-coronavirus neutralization activity against multiple SARS-CoV-2 variants and alphacoronaviruses (HCoV-229E and HCoV-NL63), demonstrating its potential for development into a broad-spectrum therapeutic candidate.