Platinum and palladium complexes as human immunodeficiency virus latency reversal agents

The Persistence of latent HIV-1 provirus and reservoirs presents a formidable challenge in human immunodeficiency virus (HIV/AIDS), numerous efforts have been made to develop vaccines and chemotherapeutic agents. However, an effective vaccine remains elusive, and existing HIV/AIDS medications do not lead to a cure. Antiretroviral therapy (ART) has been instrumental in suppressing the virus, but it cannot completely eradicate HIV due to its persistence and latency. Research is now focusing on developing latency activators, drugs that activate the virus from latent reservoirs and expose it to ART. In pursuit of finding an HIV cure, this study investigates three complexes (AE99, AE118, AE187), which involve synthetic metals coordinated with ligands, for reactivating HIV in latently infected cells. The aim is to incorporate the ‘shock and kill’ strategy into HIV therapy. This project uses metals as latency reversal agents to trigger an immune response and reactivate latent HIV infections. The drugs are assessed for toxicity on U1 cell lines and their effect on the virus. They target key transcriptional factors and modulate HIV transcription and replication pathways. Finally, the complexes are tested for their ability to neutralize a pseudo-virus (Q23) to confirm their bifunctional activity in utilizing the metals. Metal complexes were found to be nontoxic with CC50 values 57 uM for AE99, 63.0 for AE118, >100 uM for AE187 and Cisplatin 4.9 uM, induced viral production, cytokine release, infectivity and partially medication safety, Finally, through upregulation and downregulation of latent HIV, the metal complexes demonstrated a distinctive bifunctional effect.

Grantor dc:publisher

University of Pretoria

Year dc:date.issued

2024

Advisor dc:contributor.advisor

• Gama, Ntombenhle Hlengiwe

• UCTD
• Human immunodeficiency virus (HIV)
• Metal complexes
• P24 capsid
• Latency reversal agents

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

Dc Identifier Other

S2024

OAI identifier oai:identifier

oai:repository.up.ac.za:2263/97361