RESEARCH COLLABORATIONS

1. Novel drug discovery against Mycobacterium tuberculosis and SARS-Cov-2 coronavirus

Collaborating Parties:

Prof Samuel Egieyeh – School of Pharmacy, UWC
Prof Samantha Samson and Dr Melanie Grobbelaar – University of Stellenbosch

Prof Andrej Sali – University of California San Francisco, USA

Prof John Irwin – University of California San Francisco, USA

Prof Megan Shaw – Medical Biosciences, UWC

Dr Bianca Gordon – Medical Biosciences, UWC

Nature and purpose:

To identify drugs with a new mode of action against Mycobacterium tuberculosis protein

Target proteins essential for transcription and translation in SARS-CoV-2 coronavirus.

Output in the last 12 months:

Akinnuwesi A, Cloete R and Egieyeh SA, State-of-the-art Strategies to Prioritise Mycobacterium tuberculosis Drug Targets for Drug Discovery using a Subtractive Genomics Approach. Frontiers in Drug Discovery, 3, p.1254656. (2023).

Future Direction:

Draft two manuscripts one targeting Mycobacterium tuberculosis drug target Rv2196 and a

follow up article on Rv2421c to identify novel drug molecules to treat Tuberculosis

infections.

2. Structural impact of resistance associated mutations in the South African HIV-1C integrase protein

Collaborating Parties:

The late Dr Graeme Jacobs – University of Stellenbosch (deceased)

Nature and purpose:

Firstly, to understand genetic diversity in HIV-1 subtype C integrase gene in South African HIV-1 infected patients and recombinant subtype AG in Cameroonian patients. Secondly, to determine if second-line integrase inhibitors will be a viable option for South African and Cameroonian patients infected with HIV-1.

Output in the last 12 months:

None

Future Direction:

One manuscript submitted and under review focusing on the development of an automated pipeline to investigate the effects of mutations on HIV-1C and HIV-1 AG recombinant Integrase structure.

3. Prioritising mutations identified in South African Parkinson’s disease patients using structural methods

Collaborating Parties:

Prof Soraya Bardien – University of Stellenbosch

Nature and purpose:

To identify novel genes associated with Parkinson’s disease development using Whole

Exome sequencing and using structural computational methods to understand the impact of

mutations on protein structure and function.

Output in the last 12 months:

Cuttler K, de Swardt D, Engelbrecht L, et al. Neurexin 2 p.G849D variant, implicated in Parkinson’s disease, increases reactive oxygen species, and reduces cell viability and mitochondrial membrane potential in SH-SY5Y cells. J Neural Transm 129, 1435-1446 (2022). https://doi.org/10.1007/s00702-022-02548-8

Future Direction:

Two manuscripts under preparation for publication following up on neurexin and neuroligin

interaction associated with PD and another on a novel gene candidate identified in a South

African family with PD using exome sequencing.

4. Haplotype variation within South African Xhosa population and its effect on diabetic treatment

Collaborating Parties:

Prof Mongi Benjeddou – Biotechnology Department, UWC

Nature and purpose:

Understand the effect of haplotype variation on SLCAA2 transporter protein and the binding of diabetic drugs to SLCAA2 within a South African Xhosa population.

Output in the last 12 months:

None

Future Direction:

None to report.

5. Structural studies of more and less virulent coronavirus envelope proteins to understand human host interaction and severity of disease

Collaborating Parties:

Prof Burtram Fielding – Department of Medical Biosciences, UWC

Nature and purpose:

Perform topology predictions, structural modelling as well as simulation studies to understand the structural differences between four coronavirus envelope proteins and their interaction with the human host PALS1 protein.

Output in the last 12 months:

None

Future Direction:

Manuscript in preparation.

6. The identification and characterisation of DNA aptamers for application in diagnosis of infectious diseases

Collaborating Parties:

Prof Mervin Meyer – Biotechnology Department, UWC

Nature and purpose:

The aim of the research is to develop multiplex lateral flow devices (LFDs) for the detection of serum human biomarker proteins for TB and Ebola diagnosis using DNA aptamers.

Output in the last 12 months:

Martin DR, Mutombwera AT, Madiehe AM, Onani MO, Meyer M and Cloete R, 2024. Molecular modelling and simulation studies of SELEX-derived high-affinity DNA aptamers to the Ebola virus nucleoprotein. Journal of Biomolecular Structure and Dynamics, pp.1-18.

Future Direction:

To build an mysql database containing 3D structures of DNA aptamers for diagnostic purposes.

7. Ebola virus 3D database (EBOV-3D): Understanding the Ebola virus proteome and evaluating possible drug targets

Collaborating Parties: 

Dr Arun Pandurangan – Department of Medicine, University of Cambridge

Prof Placide Mbala- Kingebeni – National Institute of Biomedical Research, Democratic Republic of the Congo, University of Kinshasa

Prof/Sir Tom Blundell – Department of Medicine, University of Cambridge

Dr Hocine Bendou – Division of Computational Biology, University of Cape Town

Dr Adetayo Emmanuel Obasa – Faculty of Medicine and Health Sciences, University of Stellenbosch

Nature and purpose:

The aim of this project is to provide a user-friendly and easily accessible 3D webserver, so that end-users can navigate, inspect and download the 3D structural proteome data, visualise modelled oligomeric complexes, analyse pockets of modelled structures, and investigate Ebola virus human-protein interactions, mutations and protein–ligand docking interfaces. 

Output in the last 12 months:

None

Future Direction:

Build the postgre SQL backend of the database as well as the front end and prepare a manuscript.