Editorial: Now, the theory of Ubuntu has its space in social work

In this issue, we published short articles that show application of ubuntu in social work. We prioritized articles that showed how ubuntu could be used and applied in social work as well as those with a visual model representing ubuntu. Advances in technology and rapid growth of social media requires that we promote and use visual learning tools for social work especially for the young learner. This special issue’s objective was to accelerate use of concepts, models, theories and approaches that fill the gaps left by western approaches that are being put aside as Africa decolonises social work. Another objective was to encourage participation of young writers in decolonisation and indigenisation. In this editorial article, we define ubuntu, summarise existing ubuntu models in social work before sharing information about this special issue of the African Journal of Social Work (AJSW)

Misrecognition of the Rights of People with Epilepsy in Zimbabwe: A Social Justice Perspective

Epilepsy affects 4 to 14 people per 1,000, that is, an estimated 50 million people worldwide, making it the most common global neurological condition (Shorvon, 2009; WHO, 2016). It is more prevalent in the Global South, where 80 percent of people with epilepsy reside, due to “poorer perinatal care and standards of nutrition and public hygiene, and the greater risk of brain injury, cerebral infection, or other acquired cerebral conditions” (Shorvon, 2009, p. 3). In Africa alone, epilepsy directly affects about 10 million people (WHO, 2015). Indigenous cultural and religious misunderstanding affects the management of this neurological condition in many parts of the world, especially in Africa. This has led to misrecognition of the rights of people living with epilepsy, which leaves them socially isolated and makes it difficult for them to develop social networks and to access treatment, education and training, and employment. This chapter explores the misrecognition and misrepresentation of people with epilepsy, and associated injustices relating to dominant indigenous cultural and religious perspectives on epilepsy in Africa and consequent human rights omissions found in a study of persons with epilepsy in Harare, Zimbabwe. It provides an overview of perspectives on epilepsy in Africa and the injustices stemming from the continued exclusion of people with epilepsy in Zimbabwe. It suggests that Nancy Fraser’s (2000, 2001, 2008, 2010) theory of social justice offers a framework for understanding the injustices ensuing from the misrecognition of people with epilepsy and ends by suggesting an integrated rights-based model for epilepsy management in Zimbabwe and other African countries

Enhancing the fight against malaria : from genome to structure and activity of a G-protein coupled receptor from the mosquito, Anopheles Gambiae

Includes abstract.Includes bibliographical references (leaves 183-184).G-proton coupled receptors (GPCRs) are excellent drug targets that occupy a central position in the physiology of insects and are involved in transmission of signal from the extracellular to the intracellular side of the cell. Adipokinetic hormone receptors (AKHRs) are GPCRs that mediate physiological functions of the neurohormones, adipokinetic hormones (AKHs) that regulate mobilisation of energy reserves during mosquito flight. Ligand binding to GPCRs depends on the three dimensional (3D) structures of the receptors but to date no crystal structures of insect GPCRs are available. This work focused on building molecular models of AKHR from the genome of the malaria mosquito, identifying its binding site and studying the conformational and structural changes during molecular dynamics of the active and inactive receptor

‘We Were an Afterthought’: Corona Virus Disease 2019 (COVID-19) Pandemic in Culturally and Linguistically Diverse (CALD) Communities in New South Wales, Australia

This paper investigates the impact on Culturally and Linguistically Diverse (CALD) communities in Australia of government and community responses to the coronavirus pandemic of 2019 in the domains of education, employment, housing, social connectedness, and public health communication. Most of the examples are drawn from the state of New South Wales. In Australia, CALD refers to people from countries not classified as main English speaking. Most CALD communities reported in this article are from refugee backgrounds, are recently arrived migrants or do not use English in most of their communication. Inadequate, and in some instances, inappropriate or absent support, adversely impacts CALD communities. We used a multidisciplinary bricolage approach that draws on media, government, and community support publications and concluded that CALD communities experienced heightened pressures due to lower resource availability and poor communication. This led to disruption of support services, exposing gaps and vulnerability. The results reported here challenge Australian government, schools, community agencies, researchers to include proactively CALD community perspectives when planning and responding to such crises in future. Improving communication, pandemic response planning, addressing needs and ensuring participation are key considerations

Computational de-orphaning of Mycobacterium tuberculosis targets

Tuberculosis (TB) continues to be a major health hazard worldwide due to the resurgence of drug discovery strains of Mycobacterium tuberculosis (Mtb) and co-infection. For decades drug discovery has concentrated on identifying ligands for ~10 Mtb targets, hence most of the identified essential proteins are not utilised in TB chemotherapy. Here computational techniques were used to identify ligands for the orphan Mtb proteins. These range from ligand-based and structure-based virtual screening modelling the proteome of the bacterium. Identification of ligands for most of the Mtb Proteins will provide novel TB drugs and targets and hence address drug resistance, toxicity and the duration of TB treatment

Computational Deorphaning of <em>Mycobacterium tuberculosis</em> Targets

Tuberculosis (TB) continues to be a major health hazard worldwide due to the resurgence of drug discovery strains of Mycobacterium tuberculosis (Mtb) and co-infection. For decades drug discovery has concentrated on identifying ligands for ~10 Mtb targets, hence most of the identified essential proteins are not utilised in TB chemotherapy. Here computational techniques were used to identify ligands for the orphan Mtb proteins. These range from ligand-based and structure-based virtual screening modelling the proteome of the bacterium. Identification of ligands for most of the Mtb proteins will provide novel TB drugs and targets and hence address drug resistance, toxicity and the duration of TB treatment

TIBLE: a web-based, freely accessible resource for small-molecule binding data for mycobacterial species

TIBLE is a web-based resource that provides easy access to data on the minimal inhibitory concentrations for small molecules against several mycobacterial species, as well as the target binding and off-target predictions for Mycobacterium tuberculosis. The current version of the database holds the activity data for more than 19 000 distinct small molecules against 39 mycobacterial species, binding data for 106 Mycobacterium tuberculosis target proteins and predictions for their potential off-targets. The resource integrates disparate public data and methods to provide easy access to the minimum inhibitory concentration and binding data, facilitation of data sharing, and identification of small molecules and targets for development of anti-tuberculosis therapeutics.Wellcome Trust Seeding Drug Discovery (101134/Z/13/Z to A.P.H., T.L.B.); MRC Newton Award (RG78439 to S.M. and T.L.B.); Programme Grant (093167/Z/10/Z to T.L.B.); Cystic Fibrosis Trust Grant (RG 70975); Wellcome Trust Investigator Award (200814/Z/16/Z to T.L.B.)

Target identification of Mycobacterium tuberculosis phenotypic\textit{Mycobacterium tuberculosis phenotypic} hits using a concerted chemogenomic, biophysical and structural approach

Mycobacterium phenotypic hits are a good reservoir for new chemotypes for the treatment of tuberculosis. However, the absence of defined molecular targets and modes of action could lead to failure in drug development. Therefore, a combination of ligand-based and structure-based chemogenomic approaches followed by biophysical and biochemical validation have been used to identify targets for Mycobacterium tuberculosis phenotypic hits. Our approach identified EthR and InhA as targets for several hits, with some showing dual activity against these proteins. From the 35 predicted EthR inhibitors, eight exhibited an IC50 below 50 μM against M. tuberculosis EthR and three were confirmed to be also simultaneously active against InhA. Further hit validation was performed using X-ray crystallography yielding eight new crystal structures of EthR inhibitors. Although the EthR inhibitors attain their activity against M. tuberculosis by hitting yet undefined targets, these results provide new lead compounds that could be further developed to be used to potentiate the effect of EthA activated pro-drugs, such as ethionamide, thus enhancing their bactericidal effect.GM is grateful to the European Molecular Biology Laboratory and Marie Sklodowska-Curie Actions for funding this work. VM and MB acknowledge Bill & Melinda Gates Foundation [subcontract by the Foundation for the National Institutes of Health (NIH)] (OPP1024021). VM and MS acknowledge the European Community’s Seventh Framework Programme [grant number 260872]. GP would like to acknowledge the Wellcome Trust and the European Molecular Biology Laboratory for funding. JPO was funded by the member nation states of the European Molecular Biology Laboratory. TLB acknowledges The Wellcome Trust for funding and support (grant number 200814/Z/16/Z)

Novel inhibitors of Mycobacterium tuberculosis GuaB2 identified by a target based high-throughput phenotypic screen

High-throughput phenotypic screens have re-emerged as screening tools in antibiotic discovery. The advent of such technologies has rapidly accelerated the identification of ‘hit’ compounds. A pre-requisite to medicinal chemistry optimisation programmes required to improve the drug-like properties of a ‘hit’ molecule is identification of its mode of action. Herein, we have combined phenotypic screening with a biased target-specific screen. The inosine monophosphate dehydrogenase (IMPDH) protein GuaB2 has been identified as a drugable target in Mycobacterium tuberculosis, however previously identified compounds lack the desired characteristics necessary for further development into lead-like molecules. This study has identified 7 new chemical series from a high-throughput resistance-based phenotypic screen using Mycobacterium bovis BCG over-expressing GuaB2. Hit compounds were identified in a single shot high-throughput screen, validated by dose response and subjected to further biochemical analysis. The compounds were also assessed using molecular docking experiments, providing a platform for their further optimisation using medicinal chemistry. This work demonstrates the versatility and potential of GuaB2 as an anti-tubercular drug target

Synthesis, stereochemistry and in vitro STD NMR and in silico HIV-1 PR enzyme-binding potential of MBH-derived inhibitors

Aza-Michael reactions of a pyridine-3-carbaldehyde-derived Morita-Baylis-Hillman (MBH) adduct with various amines have afforded a series of 10 diastereomeric products, stereochemical analysis of which has been achieved using a combination of NMR (1D, 2D and NOESY) and computer modelling methods. Saturation Transfer Difference (STD) 1H NMR spectroscopy and in silico molecular docking studies have been used to explore the HIV-1 protease sub-type C enzyme binding potential of these compounds in five different HIV-1 PR enzyme receptors