Innovation Experiences from Africa-Led Drug Discovery at the Holistic Drug Discovery and Development (H3D) Centre

Abstract

As the so-called “next frontier” in global economic terms, Africa’s disease burden continues to choke and cripple economic growth across the continent. The highest burden is attributable to malaria and tuberculosis (TB), which also remain among the deadliest infectious diseases affecting mankind the world over (Malaria, 627,000 deaths; TB, 1.5 million deaths, in 2020). In achieving self-determination with respect to the health needs of all who live on the continent, Africa must align with global north efforts and be a source of health innovation. This will in part require the creation of an ecosystem of innovative pharmaceutical R&D and expanding it across the continent by scaling up through sustained performance and excellence. To this end, the Holistic Drug Discovery and Development (H3D) Centre at University of Cape Town in South Africa has risen to this challenge. Here, we highlight the innovation experiences gained at H3D, covering the advances made in our quest to contribute to a global pipeline of therapeutic interventions against malaria and TB. We discuss selected chemical series starting from their identification, structure–activity relationships, mode of action, safety, proof-of-concept studies, and lessons learned.

Investigation of the antimycobacterial activity of African medicinal plants combined with chemometric analysis to identify potential leads

“…The in vitro activity of the crude extract of C. asiaticum and its SPE-fraction 5 (F5) were phenotypically assessed against the infectious M. tuberculosis H37RvMA strain at the Holistic Drug Discovery and Development Centre (H3D), University of Cape Town, South Africa 27 . The microplate Alamar blue assay was used to determine the MIC of the extract and its fraction 28 .…”

“…Antimycobacterial assays were outsourced to the H3D Center, University of Cape Town, South Africa 27 . The MIC, i.e., concentration required to inhibit 90% of the culture of M. tuberculosis H37RvMA ATCC 27294, was determined using the slightly microplate Alamar blue assay previously described by Franzblau et al 28 .…”

Biological and Medicinal Chemistry in Africa

“…This approach is well founded, given the staggering success of the handful of well resourced, Africanled scientific operations. [27][28][29][30] The scope of these important funding instruments offers myriad opportunities, including mobility, skills transfer, incentives to return to Africa institutions, the development of emerging researchers, promoting the participation of women in science and are increasingly normalizing North-South and even South-South collaborative relationships. [31] Importantly, while still limited in number, and themselves often subject to political ebbs and flows, [32] these awards are commonly generous in value, and for the recipients, temporarily remove financial barriers to access.…”

“…Emerging out of initial paternalistic approaches to externally engage with African problems, with limited African participation, [25,26] increasingly farsighted organizations have developed funding instruments that encourage or even mandate inclusive African‐led projects. This approach is well founded, given the staggering success of the handful of well resourced, African‐led scientific operations [27–30] . The scope of these important funding instruments offers myriad opportunities, including mobility, skills transfer, incentives to return to Africa institutions, the development of emerging researchers, promoting the participation of women in science and are increasingly normalizing North‐South and even South‐South collaborative relationships [31] .…”

Forging a Future Free from Neglected Tropical Diseases

“…In LMICs, drug discovery efforts are limited, with insufficient leadership to drive innovation toward public health needs. However, promising initiatives driven out of academic institutions like the University of Cape Town Holistic Drug Discovery and Development (H3D) Centre in South Africa are working to increase capacities in drug discovery and foster scientific leadership . Yet, increased investment by local governments in both academic and industrial sectors is crucial.…”