Research leader: Prof D.Meyer
Co-investigator: Dr N Gama
Identifying novel biomarkers of HIV/AIDS through metabonomics methodologies and developing less toxic drugs and immune system modulators from natural (plants/marine organisms) and synthetic (metallodrugs/peptides) sources.
HIV/AIDS, malaria and tuberculosis compete for the position of most detrimental disease, especially in sub-Saharan Africa. To augment the problem, infections by the causative agents can occur simultaneously and the treatment of all of these diseases are currently complicated by the development and spread of drug resistant microorganisms, all of which underscores the need for improved medications. We investigate bimetallic (tandem) metallodrugs based on the platinum group metals (PGMs) with every metal center directed against or designed for activity against a specific pathogen (HIV, Mycobacterium tuberculosis, Plasmodium falciparum) or disease outcome (cervical cancer as opportunistic outcome of AIDS).
In addition to immune system disruption, HIV infection is also known to cause metabolic abnormalities. Infrared (IR) spectroscopy of serum is a quick and reagent-free methodology with which to analyse metabolic alterations such as those caused by disease or treatment providing data that is complementary to more sensitive and technically involved methods like nuclear magnetic resonance (NMR) and mass spectroscopy (MS).
Five Facts about HIV/AIDS related to HIV Research at UP:
1. Existing anti-retroviral drugs control viral replication if taken as prescribed; novel, less/non-toxic drugs are under development to decrease drug resistance and add to the arsenal available against HIV.
2. Compounds that stimulate, boost or support the immune system contributes to the fight against AIDS; these can be naturally or synthetically derived.
3. CD4 cell numbers and viral load are markers of AIDS; novel indicators of disease, infection or treatment may be derived from the effect of HIV/AIDS on the metabolic system.
4. HIV proteins and peptides induce useful humoral immune responses during natural infection and may serve as beneficial components of a complex HIV vaccine.
5. Antibodies induced by HIV proteins are used for diagnostic purposes and may develop into alternative markers of disease progression.
El Lithey M, Lall N, Hussein AA and Meyer D (2014) Cytotoxic and HIV-1enzyme inhibitory activities of Red Sea marine organisms in BMC Complementary and Alternative Medicine.2014, 14:77, DOI: 10.1186/1472-6882-14-77.
El Lithey M, Lall N, Hussein AA and Meyer D (2013) Cytotoxic, Cytostatic and HIV-1 PR Inhibitory Activities of the Soft Coral Litophyton arboreum Marine. Drugs, 11, 4917-4936; doi:10.3390/md11124917.
Kapewangolo P, HusseinA and Meyer D (2013). Inhibition of HIV-1 enzymes, antioxidant and anti-inflammatory activities of Plectranthus barbatus. Journal of Ethnopharmacology 149 (2013) 184–190.
Williams A, Steffens F, Reinecke C and Meyer D (2013). The Th1/Th2/Th17 cytokine profile of HIV-infected individuals: A multivariate cytokinomics approach, Cytokine, (61) 521-526.
Sitole L, Williams A, Meyer D (2013) Metabonomic analysis of HIV-infected biofluids, Mol Biosyst, (9)18 –28.
Williams A, Koekemoer G, Lindeque Z, Reinecke C and Meyer D (2012). Qualitative serum organic acid profiles of HIV infected individuals not on treatment, Metabolomics, Volume 8 (5) 808-818.
Masebe TM, Bessong PO, Nwobegahay JM, Ndip RN and Meyer D (2012). Prevalence of MDR1 C3435T and CYP2B6 G516T polymorphisms among HIV-1 infected South African patients, Disease Markers 32, 43-50.
Fonteh PN, Keter F, Meyer D (2011). New bis (thiosemicarbozonate) gold III complexes inhibit HIV replication at cytostaic concentrations: Potential for incorporation into virostatic cocktails, Journal of Inorganic Biochemistry, (105)1173–1180.
Fonteh PN, Keter F, Meyer D (2010). HIV Therapeutic possibilities of gold compounds, Biometals, Volume 23 (2) pg 185-196 (DOI 10.1007/s10534-010-9293-5).
Fonteh PN, Keter F, Meyer D, Guzei I, Darkwa J (2009). Tetra-chloro-(bis-(3,5-dimethylpyrazolyl)methane)gold(III)chloride: An HIV-1 reverse transcriptase and protease inhibitor, in Journal of Inorganic Biochemistry, 103 (2): 190-4.
Fonteh PN and Meyer D (2009). Novel gold(I) phosphine compounds inhibit HIV-1 enzymes. Metallomics, 1-7. DOI: 10.1039/b909036c. This journal is © the Royal Society of Chemistry.
Philippeos C, Steffens F.E and Meyer D (2009). Comparative 1H NMR-based metabonomic analysis of HIV-1 sera”, in Journal of Biomolecular NMR, 44 (3) 127-137.
Klos M, Van De Venter M, Milne PJ, Traore HN, Meyer D and Oosthuizen V (2009) In vitro anti-HIV activity of five selected South Africa medicinal plant extracts in Journal of Ethopharmacology 124, pg 182-288.
Williams A and Meyer D (2009). Desferrioxamine as immunomodulatory agent during microorganism infection, Current Pharmaceutical Design, (15) 1261-1268.
Hewer R and Meyer D (2007). Envelope-based peptides as antigens in HIV-1 immunodiagnostics. International Journal of Biotechnology, Vol 9, No’s 3-4, 277-291.
Barker BR, Parvani JG, Meyer D, Hey As, Skak K and Letvin NL (2007) IL-21 induces apoptosis of antigen-specific CD8+ T Lymphocytes in Journal of Immunology; 179 (6): 3596-603
Applying analytical (chemistry and physics) methodology to the understanding of HIV/AIDS and its effect on the metabolic and immune systems.
Identifying novel biomarkers of HIV/AIDS using metabonomics methodologies (NMR, MS, IR and Raman spectroscopies).
Developing novel metallodrugs (containing metals abundant in South Africa) and isolated compounds from plants and marine organisms with activity against HIV enzymes, other viral or opportunistic infection targets and/or immune stimulatory effects.
Investigating virus and host-derived envelope peptides for immune stimulatory activities.
Partnerships and Collaborations:
1. Prof J. Darkwa (Chemistry Department, University of Johannesburg), Prof E. Nordlander (Chemistry, Lund University)
2. Prof C.Reinecke (Centre for Human Metabolomics, North West University); Prof TR McKnight (Radiology and Imaging, University of California, San Francisco)
3. Prof B, Kana (NHLS, Wits)