RESEARCH COLLABORATIONS

1. Novel drug discovery against Mycobacterium tuberculosis

Collaborating Parties:
Prof Alan Christoffels – SANBI, UWC
Prof Samantha Samson and Dr Melanie Grobbelaar – Stellenbosch University

Nature and purpose:
To identify drugs with a new mode of action against Mycobacterium tuberculosis protein
targets.

One published article:  Cloete R, Shahbaaz M, Grobbelaar M, Sampson SL, Christoffels A. In silico repurposing of a Novobiocin derivative for activity against latency associated Mycobacterium tuberculosis drug target nicotinate-nucleotide adenylyl transferase (Rv2421c). PLoS One. 2021 Nov 2;16(11):e0259348. doi: 10.1371/journal.pone.0259348. PMID: 34727137.
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 – Stellenbosch University (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:
Mikasi SG, Isaacs D, Chitongo R, Ikomey GM, Jacobs GB, Cloete R. Interaction analysis of
statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. BMC Infectious Diseases. 2021;21(1):1–12.

Future Direction:
Two manuscripts in preparation, one focusing on the effect of Raltegravir resistant mutations on the HIV-1C integrase structure and another 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 – Stellenbosch University

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:
1) Sebate B, Cuttler K, Cloete R, Britz M, Christoffels A, Williams M, et al. Prioritization of
candidate genes for a South African family with Parkinson’s disease using in-silico tools. PloS
one. 2021;16(3):e0249324.
2) Cuttler K, Hassan M, Carr J, Cloete R, Bardien S. Emerging evidence implicating a role for
neurexins in neurodegenerative and neuropsychiatric disorders. Open Biol. 2021
Oct;11(10):210091. doi: 10.1098/rsob.210091. Epub 2021 Oct 6. PMID: 34610269; PMCID:
PMC8492176.

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:
Manuscript submitted for publication.

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 characterization 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, Sibuyi NR, Dube P, et al. Aptamer-Based Diagnostic Systems for the Rapid
Screening of TB at the Point-of-Care. Diagnostics (Basel, Switzerland). 2021 Jul;11(8). DOI:
10.3390/diagnostics11081352. PMID: 34441287; PMCID: PMC8391981.
https://doi.org/10.3390/diagnostics11081352

Future Direction:
To draft a research article on the identification of potential human biomarkers that can be
targeted by DNA aptamers for Tuberculosis diagnosis. Complete an in silico research paper
on the development of novel DNA aptamers against Ebola virus nucleoproteins as well as
drafting a review article on Ebola virus diagnostic tools.