Insight investigation of rilpivirine and compounds from mushrooms as feline immunodeficiency virus reverse transcriptase inhibitors using molecular dynamics simulations and quantum chemical calculations

Abstract

ABSTRACT Because the pathogenesis of feline immunodeficiency virus (FIV) is similar to the human immunodeficiency virus (HIV) infection, FIV is also used as a model for the drug discovery of HIV. A known HIV reverse transcriptase (RT) drug, i.e. rilpivirine, was found to inhibit FIV RT. However, there is no potent vaccine and drug for FIV treatment. In this work, the binding of rilpivirine in FIV RT is investigated. Moreover, virtual screening was applied to search from an in-house mushroom database namely ‘Bacmushbase’ to look for the new candidates from mushrooms. Two compounds from cordyceps, cordyceamides A and B, were found to be possible to bind with FIV RT which were supported by the previous report about their potential extracts for inhibiting FIV RT. Consequently, molecular dynamics simulations and quantum chemical calculations were applied to confirm their binding capabilities. From MM-PBSA and QM/MM calculations, the average binding free energies of cordyceamide A are better than those of rilpivirine. Moreover, residual interaction energies revealed the important H-bond, H-pi and pi-pi interactions to residues in the binding pocket. From the results, the binding interaction to FIV RT will be useful for FIV drug development in the future.