DNA aptamers specifically bind to SARS-CoV-2 N protein. A The expression and purification of SARS-CoV-2 N, S-RBD-Fc and 3CLpro proteins with a His-Ni–NTA system. B A sketch map for the ELAA. Briefly, the N protein was serially diluted and coated on the plates. After blocking, the N protein was detected with biotinylated ssDNA aptamers followed by HRP conjugated Avidin system. C Aptamer 1, 2 and 3 binds SARS-CoV-2 N protein in an Enzyme-Linked Aptamer Binding Assay (ELAA). BSA, SARS-CoV-2 S-RBD and 3CLpro proteins served as negative controls. Aptamer n.c. binds to none of the tested proteins. D Detection of N protein in diluted human serum by ssDNA aptamers. E ssDNA aptamer 2 specifically detects SARS-CoV-2 N protein in Western Blot assay. Antibody against N protein served as controls. Serially diluted N proteins (10 μg, 1μg, and 0.1μg) and 10 μg of 3CLpro protein were probed with N Aptamer 2 and N antibody, respectively. The data shown are representative of 3 independent experiments.