The HIV-1 entry inhibition capabilities of Isoflavones

The availability of treatment for HIV infection has resulted in a drastic increase in the life expectancy of infected individuals. However, the current therapeutics fall short in many areas. A considerable 60% of treated individuals will show minor cognitive disorders due to infection, immune reconstruction inflammatory syndrome occurs in a high number of individuals of African descent as a treatment side-effect, and treatment resistance occurs commonly both with long-term infected individuals and newly infected individuals. This all highlights the need for continued research into combating the HIV pandemic. This research investigated the anti-HIV activity of five novel Isoflavones. Isoflavones and similar compounds have been extensively researched for their ability to hinder HIV reproduction through multiple routes of antagonism in the HIV life cycle but with little research in HIV entry inhibition. In this study, the anti-HIV activity of the isoflavones was quantified through the generation of IC50 values using a luciferase reporter assay. Evidence for potential entry-inhibiting activity was generated through time-of-addition studies and the potential drug targets were hypothesised using computational docking studies. All the Isoflavones were shown to inhibit HIV replication in the lower micromolar regions with IC50 values ranging from 6.2 to 10.6 μM. Two of the isoflavones, B and C, were shown to possess significant entry inhibitory activity of HIV-1 through time-of-addition studies (0.041 and 0.007, respectively ). Docking studies illustrate the potential for these compounds to act through gp120 antagonism and provide the framework for future drug development using these compounds as gp120 anchoring regions.

Grantor dc:publisher

University of Pretoria

Year dc:date.issued

2023

Advisor dc:contributor.advisor

• Gama, Ntombenhle Hlengiwe

• UCTD
• Biochemistry
• Human immunodeficiency virus (HIV)
• Drug discovery
• Entry inhibitors
• Drug design
• Isoflavones
• Flavonoids
• Gp120

Statement dc:rights

• © 2023 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria.

Language dc:language.iso

en

DOI

https://doi.org/10.25403/UPresearchdata.24650211

Identifier URI

DOI: https://doi.org/10.25403/UPresearchdata.24650211.v1

Dc Identifier Other

A2024

OAI identifier oai:identifier

oai:repository.up.ac.za:2263/93769