J Vet Sci.  2023 Sep;24(5):e67. 10.4142/jvs.22326.

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

• Rattanabunyong S
• Choengpanya K
• Suwattanasophon C
• Kiriwan D
• Wolschann P
• Lamtha T
• Shaikh AR
• Rattanasrisomporn J
• Choowongkomon K

• KMID: 2546801
• DOI: http://doi.org/10.4142/jvs.22326

Abstract

Background
Feline immunodeficiency virus (FIV) causes an acquired immunodeficiencylike 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.

Keyword

HIV; FIV; NNRTI; nevirapine; efavirenz; rilpivirine