IN SILICO DESIGN OF AMINO ACIDS-FUNCTIONALIZED IMIDAZOLES AS INHIBITORS OF DENGUE VIRUS NS3 AND NS5 PROTEINS
Keywords:
diseño de fármacos; acoplamiento molecular; ADME+T; DFT; virus del dengue; imidazoles funcionalizados con aminoácidos.Abstract
252 amino acid-functionalized imidazoles were designed to evaluate their potential as
inhibitors using computational techniques. An analysis of the ADME+T profiles indicates
that compounds derived from the polar amino acids Ser and Thr are the most favorable as
drug candidates. Of these compounds, four (Ser-A22, Thr-A22, Ser-A35 and Thr-A35) stand
out as candidates for inhibitors of proteins NS3 in their helicase domain and NS5 in their
methyltransferase domain. For the NS2B-NS3Pro and NS5RdRp domains, the results are not
encouraging. An analysis of the electron densities of these four compounds by DFT showed
similarity with reference inhibitors in terms of frontier orbitals, reactivity and electrostatic
potential surfaces, which explains the strength of the binding of these compounds with viral
proteins
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Copyright (c) 2025 Yonatan Mederos-Núñez, Yoan A. Pérez-Garmury, Armando Ferrer-Serrano, Julio A. Rojas-Vargas, América García-López
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