In-Vitro Study of HIV-derived Reverse Transcriptase Inhibition

Abstract

Introduction:: HIV utilizes a reverse transcriptase (RT) enzyme to convert the HIVRNA into DNA. Inhibition of the reverse transcription mechanism of HIV-RT may serve as a potential therapeutic approach to impede the proliferation of HIV in those who are infected. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are a type of medication that directly and non-competitively bind to the allosteric site of HIV-RT, inhibiting its polymerase activity. Aim:: This study was aimed at the synthesis of hydrazine derivatives and their evaluation for HIV- reverse transcriptase inhibition using RT-qPCR-based assay. Objective:: The objective of this study was to determine the HIV- reverse transcriptase inhibition using chemical compounds as non-nucleoside reverse transcriptase inhibitors in RT-qPCR. Methods:: This study involved the synthesis of five distinct hydrazine derivatives, which were subsequently tested for their capacity to inhibit HIV-RNA polymerization by targeting HIVderived reverse transcriptase. For the determination of the study assay, commercially available HIV-RT was subjected to treatment with derivatives and utilized in an RT-qPCR experiment to determine the activity or inhibitory effects of HIV-RT for HIV-RNA polymerization. Results:: The in-vitro assay results demonstrated a reduction in viral load due to suppression of reverse transcriptase activity when compared to the pre-quantified values obtained from untreated RT. Among the five compounds, 4-N, N-dimethylamino benzaldehyde hydrazine (C18H22N4) had the highest ability to suppress HIV-RT. This molecule reduced HIV-RNA reverse transcription by more than 90% during RT-qPCR, which is a novel and promising strategy. Conclusion:: N, N-dimethylamino benzaldehyde hydrazine (C18H22N4) can suppress the activity of HIV-RT, and this effect becomes more pronounced as the concentration of the compound increases.