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Faculty of Health Sciences (FHS) graduate students Khumoekae Richard and Cole Schonhofer recently showing how an African natural product enhances HIV-1 latency reversal. Acting as the lead authors for this research, they screened 216 compounds from the pan-African Natural Products Library and identified the product knipholone anthrone (KA) as a latency-reversal agent (LRA).

People living with HIV/AIDS can control viremia by taking combination antiretroviral therapies, but existing drugs do not affect the latent HIV reservoirs, which exist in a small number of cells in the body and are invisible to the immune system. These reservoirs can reactivate at any time to produce new virus, which means that people living with HIV have to take antiretrovirals for life.

In their research, the use of LRAs KA or anthralin, a structurally similar synthetic compound, induced HIV reservoir-containing cells to produce HIV. This approach, often termed the 鈥渟hock-and-kill鈥� strategy, works by stimulating latent reservoirs to produce new viruses so that the immune system can recognize these cells and eliminate them. This is also done in the presence of antiretrovirals to prevent further HIV spread.

Their supervisor, FHS adjunct professor Ian Tietjen, points out that 鈥渟hock-and-kill鈥� drugs to date have not had much efficacy in clinical trials so far, and that there is a need to find new agents that can enhance the effects of existing 鈥渟hock-and-kill鈥� drugs in clinics.

鈥淩ichard and Schnohofer were able to show that both of the LRAs enhance the activity of several different 鈥榮hock-and-kill鈥� drugs that are being investigated in clinical trials,鈥� Tietjen says. 鈥淲e propose that combination therapies that involve multiple drugs might be the way to go to sufficiently enhance viral reservoir expression and minimize drug toxicities.鈥�

Originally from Botswana, Richard is a Queen Elizabeth II (QE2) Diamond Jubilee scholarship recipient and Sub-Saharan African Network for TB/HIV Research Excellence (SANTHE) scholar. This project gave him the chance to work with HIV cure-directed research - a top priority for Botswana - and chemical compounds that originate from medicinal plants in Botswana and elsewhere in Southern Africa. He is currently doing field-work in Botswana with local traditional healers to document and characterize medicinal plants used for HIV/AIDS management and also to treat COVID.

Schonhofer, an MSc graduate of Tietjen鈥檚 lab, was closely involved with much of the molecular and cell biology in their research. FHS PhD students Natalie Kinloch and Aniqa Shahid also contributed to this work.

The research team hopes that these types of efforts will eventually identify new leads for HIV, SARS-CoV-2, and other antivirals to characterize at the molecular/cell biology level and improve therapeutic options for both local communities in Botswana and perhaps elsewhere. Their research will also help inform HIV research regarding factors involved in modulating HIV latency and how to target them, and which factors and pathways ought to be further investigated.

鈥淥ur research is important because it brings new players in the field, as in novel LRAs with the potential to enhance and improve the 鈥渟hock-and-kill鈥� approach, which is one of the hypothetical strategies thought to help in the search for an HIV cure,鈥� Richard emphasizes. 鈥淚t鈥檚 a new discovery and should give us hope.鈥�