Discovery of the Sandwich type COVID-19 Nucleocapsid Protein DNA Aptamers

Here, we represent the first DNA aptamers targeted to COVID-19 nucleocapsid protein (Np). Np is one of the most abundant structural proteins and serves as a diagnostic marker for accurate and sensitive detection of the COVID-19. After five rounds of selection, we obtained four DNA sequences with the affinity below 5 nM. The best one displays a superb binding performance to Np with a Kd value of 0.49 nM. Interestingly, we found that four pairs of aptamers could bind to Np successively, suggesting a sandwich-type interaction. Using these sandwiched aptamers in ELISA and colloidal gold immunochromatographic strips, we were able to detect Np at tens of pM level. The results demonstrate that aptamers are powerful molecular tools for virus detection, diagnosis, and antiviral therapy.