The effect of HIV protease gene mutations to protease inhibitor drugs resistance in Papua patients: In silico analysis

Abstract

The use of phenotypic assay requires laborious work to culture HIV isolates to observe the phenotypic change of the virus in the presence of antiretroviral drugs. The genotypic approach may rely on the secondary data of documented mutations that are responsible for phenotypic alterations to antiretroviral-resistant HIV. HIV genomes were extracted from patients’ plasma, which was subsequently subjected to RT-PCR and Sanger sequencing. The obtained HIV genome sequencing data were analyzed for mutation detection. Three-dimensional (3D) structures of mutant HIV protease were constructed using FoldX software. The binding affinity of the mutant HIV protease with protease inhibitor drugs (Saquinavir, Ritonavir, Nelfinavir, Indinavir, and Lopinavir) was analyzed using AutoDock Vina. There were 90 patients involved in this study. The patients attended the Voluntary Counseling Test (VCT) of Mitra Masyarakat Hospital in Mimika, Papua, Indonesia. Among recruited subjects, the HIV genomes corresponding to the protease-encoded gene of 30 patients were successfully sequenced. There was only one patient (RSMM_70) infected with HIV harboring minor mutations (L10V, I15V, M36I, and R41K) in the protease-encoded gene that was not a new finding mutation. The 3D structure showed that the hydrophobicity and stability of mutant HIV protease were different from the wild genotype. Docking analysis showed decreasing binding affinity of the mutant HIV protease to the protease inhibitor drugs, which may lead to the alteration of inhibitory effectiveness. In silico docking, the analysis may provide an alternative approach to predict the effect of minor mutations in the HIV protease gene on the effectiveness of protease inhibitor drugs.