The highly conserved RNA-binding specificity of nucleocapsid protein facilitates the identification of drugs with broad anti-coronavirus activity.

We performed the high-throughput RNA-SELEX (HTR-SELEX) to determine the RNA-binding specificity of the N proteins of various SARS-CoV-2 variants as well as other β-coronaviruses and showed that N proteins could bind two unrelated sequences, both of which were highly conserved across all variants and species. We purified nucleocapsid proteins of SARS-CoV-2 and other β-coronaviruses, by performed HTR-SELEX, we found it has strong and reproducible RNA sequence specificity.