Análise computacional do potencial de interação entre os medicamentos balapiravir, ivermectina e prednisolona com nanopartículas de prata num possível tratamento contra dengue

Abstract

Dengue is one of the main arboviruses that affects humans, with some of the main symptoms being pain, fever, nausea, vomiting and diarrhea, which can lead to severe shocks and hemorrhages, with the possibility of death. There is still no globally licensed antiviral treatment or vaccines for the treatment of the four dengue serotypes. The aim of this work is to analyze the molecules of balapiravir, ivermectin and prednisolone as possible drugs to be used in the treatment of dengue, when carried in the body adsorbed on silver nanoparticles, since these nanomaterials have promising physical, chemical and biological properties. For this, the structures of the three molecules were optimized using the hybrid functional B3LYP and the base 6-311+G(d,p). Molecular Dynamics simulations were carried out in the GROMACS program, with the CHARMM36 force field. The structures of the three molecules were generated and optimized, and the respective frontier orbitals, HOMO and LUMO, were generated. With these, the interaction sites of the molecule with the silver nanoparticle were determined. The RMSD analysis showed that only one replicate of the system containing ivermectin did not reach equilibrium, while the three replicates of the systems containing balapiravir and prednisolone reached equilibrium respectively at times 45 and 30 ns. The IPE analysis showed that the system containing balapiravir had the best interaction, with an average energy value equal to -3565.00 kJ mol-1. RDF analysis showed that the prednisolone molecule has the highest probability density of interacting with the silver nanoparticle. The SDF analysis, in agreement with the RDF, showed the highest density of molecules around the nanoparticle for the system containing prednisolone.