Herein, we have generated ssRNA aptamers to inhibit SARS-CoV-2 M pro , a protease necessary for the SARS-CoV-2 coronavirus replication. Because there is no aptamer 3D structure currently available in the databanks for this protein, first, we modeled an ssRNA aptamer using an entropic fragment-based strategy. We refined the initial sequence and 3D structure by using two sequential approaches, consisting of an elitist genetic algorithm and an RNA inverse process. We identified three specific aptamers against SARS-CoV-2 M pro , called MApta pro , MApta pro -IR1, and MApta pro -IR2, with similar 3D conformations and that fall in the dimerization region of the SARS-CoV-2 M pro necessary for the enzymatic activity. Through the molecular dynamic simulation and binding free energy calculation, the interaction between the MApta pro -IR1 aptamer and the SARS-CoV-2 M pro enzyme resulted in the strongest and the highest stable complex; therefore, the ssRNA MApta pro -IR1 aptamer was selected as the best potential candidate for the inhibition of SARS-CoV-2 M pro and a perspective therapeutic drug for the COVID-19 disease.
【저자키워드】 COVID-19, single strand RNA aptamer, prediction of 3D RNA aptamer structure, aptamer-protein interaction, aptamers virtual screening, aptamer-protein free energy calculation, 【초록키워드】 SARS-CoV-2, coronavirus, Genetic, protease, binding free energy, free energy, COVID-19 disease, RNA, Protein, Algorithm, molecular, 3D structure, Genetic algorithm, Interaction, Coronavirus replication, the strongest, best, enzymatic activity, approaches, enzyme, Perspective, M pro, sequence, conformation, ssRNA, initial, highest, inhibit SARS-CoV-2, the SARS-CoV-2, therapeutic drug, was selected, 【제목키워드】 Dynamics, aptamer, Simulation, ssRNA, the SARS-CoV-2,