in silico analysis of ivermectin interaction with nf-κb, mapk10, and mapk14 inflammatory agents as a candidate for treatment of covid-19 disease

Background: coronavirus disease 2019 (covid-19) is a human viral infectious disease caused by a coronavirus, known for its high transmission rate. as there is no specific drug for covid-19 treatment, therapy is primarily symptomatic. ivermectin, an fda-approved antiparasitic agent, has recently shown antiviral activity against a broad range of viruses.objectives: previous studies have indicated that ivermectin, as an inhibitor of inflammation, could be useful in treating covid-19. methods: in this study, we evaluated the structural characteristics of ivermectin-(nf-κb/mapk10/mapk14) complexes using molecular docking and molecular dynamics (md) simulation methods. the docking process was performed to determine the best conformation of the complexes. complexes with the best binding energies were selected as models for the md simulation process. furthermore, the structural (rmsd, h-bond) properties and interactions of the complexes were evaluated. additionally, to calculate the binding free energy, pmf and mmpbsa calculations were carried out. results: the molecular docking results showed that the binding energy of the ivermectin-nf-κb complex was higher than that of the other two complexes. moreover, the md simulation results for the ivermectin-nf-κb complex demonstrated that the complex equilibrated after 10 ns, and the number of h-bonds increased during the simulation. the binding energy of the ivermectin-nf-κb complex was calculated as 3.3 kcal/mol. conclusions: ivermectin binds to nf-κb with high affinity, suggesting that this protein can be an appropriate drug target to decrease inflammation, confirming the anti-inflammatory activity of ivermectin. thus, ivermectin could be a good candidate for treating sars-cov2 infections.