De novo ssRNA Aptamers against the SARS-CoV-2 Main Protease: In Silico Design and Molecular Dynamics Simulation |
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| Authors: | Francesco Morena Chiara Argentati Ilaria Tortorella Carla Emiliani Sabata Martino |
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| Affiliation: | 1.Department of Chemistry, Biology and Biotechnology, University of Perugia, Via del Giochetto, 06123 Perugia, Italy; (C.A.); (I.T.); (C.E.);2.Centro di Eccellenza CEMIN (Materiali Innovativi Nanostrutturali per Applicazioni Chimica Fisiche e Biomediche), University of Perugia, 06123 Perugia, Italy |
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| Abstract: | Herein, we have generated ssRNA aptamers to inhibit SARS-CoV-2 Mpro, 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 Mpro, called MAptapro, MAptapro-IR1, and MAptapro-IR2, with similar 3D conformations and that fall in the dimerization region of the SARS-CoV-2 Mpro necessary for the enzymatic activity. Through the molecular dynamic simulation and binding free energy calculation, the interaction between the MAptapro-IR1 aptamer and the SARS-CoV-2 Mpro enzyme resulted in the strongest and the highest stable complex; therefore, the ssRNA MAptapro-IR1 aptamer was selected as the best potential candidate for the inhibition of SARS-CoV-2 Mpro and a perspective therapeutic drug for the COVID-19 disease. |
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| Keywords: | COVID-19 single strand RNA aptamer prediction of 3D RNA aptamer structure aptamer-protein interaction aptamers virtual screening aptamer-protein free energy calculation |
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