Browsing by Author "Schoeman, Dewald"
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Item The flexible, extended coil of the pdz-binding motif of the three deadly human coronavirus e proteins plays a role in pathogenicity(MDPI, 2022) Schoeman, Dewald; Cloete, Ruben; Fielding, Burtram C.The less virulent human (h) coronaviruses (CoVs) 229E, NL63, OC43, and HKU1 cause mild, self-limiting respiratory tract infections, while the more virulent SARS-CoV-1, MERS-CoV, and SARS-CoV-2 have caused severe outbreaks. The CoV envelope (E) protein, an important contributor to the pathogenesis of severe hCoV infections, may provide insight into this disparate severity of the disease. We, therefore, generated full-length E protein models for SARS-CoV-1 and -2, MERS-CoV, HCoV-229E, and HCoV-NL63 and docked C-terminal peptides of each model to the PDZ domain of the human PALS1 protein. The PDZ-binding motif (PBM) of the SARS-CoV-1 and -2 and MERSCoV models adopted a more flexible, extended coil, while the HCoV-229E and HCoV-NL63 models adopted a less flexible alpha helix.Item Human coronaviruses: counteracting the damage by storm(MDPI Viruses, 2021) Schoeman, Dewald; Fielding, Burtram C.Over the past 18 years, three highly pathogenic human (h) coronaviruses (CoVs) have caused severe outbreaks, the most recent causative agent, SARS-CoV-2, being the first to cause a pandemic. Although much progress has been made since the COVID-19 pandemic started, much about SARS-CoV-2 and its disease, COVID-19, is still poorly understood. The highly pathogenic hCoVs differ in some respects, but also share some similarities in clinical presentation, the risk factors associated with severe disease, and the characteristic immunopathology associated with the progression to severe disease. This review aims to highlight these overlapping aspects of the highly pathogenic hCoVs—SARS-CoV, MERS-CoV, and SARS-CoV-2—briefly discussing the importance of an appropriately regulated immune response; how the immune response to these highly pathogenic hCoVs might be dysregulated through interferon (IFN) inhibition, antibody-dependent enhancement (ADE), and long non-coding RNA (lncRNA); and how these could link to the ensuing cytokine storm. The treatment approaches to highly pathogenic hCoV infections are discussed and it is suggested that a greater focus be placed on T-cell vaccines that elicit a cell-mediated immune response, using rapamycin as a potential agent to improve vaccine responses in the elderly and obese, and the potential of stapled peptides as antiviral agents.Item In vitro acetylcholinesterase inhibitory activity and chemical composition of the dichloromethane extracts of the leaves and inflorescences of the tumbleweed, Trachyandra laxa (N.E.Br.) Oberm. var. rigida (Suesseng.) Roessl(South African Journal of Botany, 2022) Van Wyk, Hedwig M; Schoeman, Dewald; Kwembeya, EzekeilTrachyandra laxa, which belongs to the family Asphodelaceae, is a poisonous geophyte, often consumed by livestock, particularly when pastures are poor. Ingestion of T. laxa by livestock causes paresis and paralysis of the animals. However, the chemical composition of this plant has never been studied before and its toxic components are still unknown. In this study, an acetylcholinesterase (AChE) inhibition assay of different extracts of the parts of Trachyandra laxa (N.E.Br.) Oberm. var. rigida (Suesseng.) Roessl. revealed that the DCM extracts possess the highest AChE inhibitory activity. In addition, using qualitative phytochemical tests, it was determined that all the plant parts contain polyphenols and tannins, while only the leaves contain flavonoids. Saponins were detected in all plant parts, except in the flowers and anthraquinones were detected in all plant parts expect the roots. Using GC MS analysis, 13 volatile constituents were identified in the DCM extracts of the leaves and inflorescences, including a,b-unsaturated lactones, carboxylic acids and esters, a diterpenoid, phytol, and a phytosterol, b-sitosterol. Of particular interest are the a,b-unsaturated lactones, which were identified as dihydroactinidiolide (DHA) and its hydroxylated analogue, hydroxy‑DHA, as well as phytol, a diterpenoid. DHA and phytol have been reported to possess potent AChE inhibition activity. It is therefore plausible that these compounds and potentially also hydroxy‑DHA could contribute to the AChE inhibitory activity of the DCM extracts, and thus the neurotoxicity of T. laxa var. rigida.Item Is there a link between the pathogenic human Coronavirus envelope protein and immunopathology? A review of the literature(Frontiers Media S.A., 2020) Fielding, Burtram Clinton; Schoeman, DewaldSince the severe acute respiratory syndrome (SARS) outbreak in 2003, human coronaviruses (hCoVs) have been identified as causative agents of severe acute respiratory tract infections. Two more hCoV outbreaks have since occurred, the most recent being SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19). The clinical presentation of SARS and MERS is remarkably similar to COVID-19, with hyperinflammation causing a severe form of the disease in some patients. Previous studies show that the expression of the SARS-CoV E protein is associated with the hyperinflammatory response that could culminate in acute respiratory distress syndrome (ARDS), a potentially fatal complication. This immunemediated damage is largely caused by a cytokine storm, which is induced by significantly elevated levels of inflammatory cytokines interleukin (IL)-1β and IL-6, which are partly mediated by the expression of the SARS-CoV E protein.Item Leptin deficiency, caused by malnutrition, makes you susceptible to sars-cov-2 infection but could offer protection from severe Covid-19(American Society for Microbiology, 2021) Schoeman, Dewald; Fielding, Burtram C.In much of the developing world, severe malnutrition is the most prevalent cause of immunodeficiency and affects up to 50% of the population in some impoverished communities. As yet, we do not know how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will behave in populations with immunodeficiency caused by malnourishment. Interestingly, researchers are now speculating that, in some instances, a defective cellular immune system could paradoxically be a protective factor against severe disease in certain patients contracting SARS-CoV and SARS-CoV-2. This could be linked to the absence of T-cell activation. Based on available information presented here, it is plausible that the hyperimmune response, and subsequent cytokine storm often associated with severe coronavirus disease 2019 (COVID-19), could be “counteracted” by the defective immune response seen in individuals with malnutrition-induced leptin deficiency. In this paper, we proposed a theory that although those with malnutrition-linked leptin deficiency are at risk of SARS-CoV-2 infection, they are at lower risk of developing severe COVID-19.Item Pathogenic human Coronavirus envelope protein: A clear link to Immunopathology?(MPDI, 2020) Schoeman, Dewald; Fielding, Burtram C.Since the severe acute respiratory syndrome (SARS) outbreak in 2003, human coronaviruses (hCoVs) have been identified as causative agents of severe acute respiratory tract infections. Two more hCoV outbreaks have since occurred, the most recent being SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19). The clinical presentation of SARS and MERS is remarkably similar to COVID-19, with hyperinflammation causing a severe form of the disease in some patients.Item Potamonautes spp. As a bioindicator for oestrogenic endocrine disrupting chemicals(University of the Western Cape, 2017) Schoeman, Dewald; Pool, Edmund J.Environmental pollutants, such as endocrine disrupting chemicals (EDCs), are a health concern as they can adversely affect animal health by interfering with the normal function of hormones. Oestrogenic EDCs can cause adverse developmental and reproductive effects by mimicking or inhibiting endogenous oestrogens. However, these effects are difficult to detect as they often only manifest long after the initial exposure. Vitellogenin (VTG) is the precursor to the major yolk protein vitellin (Vn) and is produced by egg laying females in response to oestrogens. The VTG gene is also present in males, but silent. Thus, the presence of VTG and Vn in animals, as well as the synthesis thereof in response to oestrogens, can serve a dual purpose in biomonitoring experiments. These proteins can be monitored over a period of time to establish the reproductive cycle of an organism and can also serve as a biomarker for oestrogenic pollutants.