Biochemical and structural comparisons of non-nucleoside reverse transcriptase inhibitors against feline and human immunodeficiency viruses

Abstract

Background: Feline immunodeficiency virus (FIV) causes an acquired immunodeficiency-like syndrome in cats. FIV is latent. No effective treatment has been developed for treatment the infected cats. The first and second generations non-nucleoside reverse transcriptase inhibitors (NNRTIs) for HIV treatment nevirapine (NVP) and efavirenz (EFV) and rilpivirine (RPV) were used to investigate the potential of NNRTIs for treatment of FIV infection. Objective: This study aims to use experimental and in silico approaches to investigate the potential of NNRTIs NVP EFV and RPV for inhibition of FIV reverse transcriptase (FIV-RT). Methods: The FIV-RT and human immunodeficiency virus reverse transcriptase (HIV-RT) were expressed and purified using chromatography approaches. The purified proteins were used to determine the IC50 values with NVP EFV and RPV. Surface plasmon resonance (SPR) analysis was used to calculate the binding affinities of NNRTIs to HIV-RT and FIV-RT. The molecular docking and molecular dynamic simulations were used to demonstrate the mechanism of FIV-RT and HIV-RT with first and second generation NNRTI complexes. Results: The IC50 values of NNRTIs NVP EFV and RPV against FIV-RT were in comparable ranges to HIV-RT. The SPR analysis showed that NVP EFV and RPV could bind to both enzymes. Computational calculation also supports that these NNRTIs can bind with both FIV-RT and HIV-RT. Conclusions: Our results suggest the first and second generation NNRTIs (NVP EFV and RPV) could inhibit both FIV-RT and HIV-RT. ? 2023 The Korean Society of Veterinary Science