Аннотация:DNA aptamers are oligonucleotides specifically bound to target molecules that serve as antibodies of nucleic acid nature. We identified an aptamer named MEZ that is highly specific to the receptor-binding domain, RBD, of SARS-CoV-2 spike protein from the Wuhan-Hu-1 strain. The SELEX procedure was utilized to enrich the initial 31-mer oligonucleotide library with the target aptamer. The aptamer identification was performed by the novel protocol based on nanopore sequencing developed in this study. The MEZ aptamer was chemically synthesized and tested for binding with SARS-CoV-2 RBD of the Spike protein from different strains. The Kd is 6.5 nM for complex with the RBD from the Wuhan-Hu-1 strain that is comparable with known aptamers, however the MEZ aptamer is smaller than known analogs. The proposed aptamer is highly selective to the RBD from the Wuhan-Hu-1 strain and does not form complexes with RBD from Beta, Delta and Omicron strains. Experimental and theoretical studies together revealed the molecular mechanism of the aptamer binding. The aptamer occupies the same binding site as the ACE2 when bound to the RBD. The 3’-end of MEZ aptamer is important for the complex formation and is responsible for discrimination of the RBD from a specific strain. The 5’-end is responsible for the formation of a loop in the 3D structure of aptamer that is important for proper binding.