Programme: BIochemistry
Permanent URI for this collectionhttp://itsupport.cu.edu.ng:4000/handle/123456789/28779
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Item Targeting invasion-associated proteins PfSUB2 and PfTRAMP in Plasmodium falciparum: identification of potential inhibitors via molecular docking(BMC Infectious Diseases, 2025) Okafor, Esther. O.; Bella-Omunagbe, Mercy; Elugbadebo, Temitope; Dokunmu, Titilope M.; Adebiyi, EzekielPlasmodium falciparum subtilisin-like protease 2 (PfSUB2) is responsible for processing Plasmodium falciparum thrombospondin-related apical merozoite protein (PfTRAMP). These proteins are essential for asexual blood stage growth and RBC invasion and have, therefore, been identified as potential drug targets. This study predicted the three-dimensional structure of PfSUB2 and PfTRAMP and identified potential inhibitors using molecular docking methods. Five hundred nineteen compounds were docked against both proteins with AutoDock Vina in PyRx. Compounds 139,974,934 and 154,414,021 exhibited better binding affinities when compared to the standard inhibitors, PMSF, which highlights them as suitable inhibitors and potential antimalarials targeting PfTRAMP and PfSUB2. It also highlights 155,204,487 as a compound with dual antimalarial target potential, exhibiting a better binding affinity to PfTRAMP and PfSUB2. The study recommends 139,974,934, 154,414,021, and 155,204,487 as possible compounds for antimalarial drug development.Item Interleukin-6-Mediated Inflammation on Telomere Length Dynamics in Malaria Infection(NIPES-Journal of Science and Technology, Research Vol. 7, 2025) Afolabi, Israel Sunmola; Fiamitia, Carrin—Malaria, an infectious disease caused by Plasmodium species, remains a significant global health concern, contributing to millions of deaths annually, particularly in endemic regions. In 2023, approximately 263 million malaria cases were reported, according to the World Malaria Report. Malaria infection triggers an inflammatory response critical to its pathogenesis, with cytokines as potential biomarkers and therapeutic targets. Among these, interleukin-6 (IL-6) plays a crucial role in disease progression, immune regulation, and severity. Emerging evidence suggests that chronic inflammation induced by malaria infection may accelerate telomere attrition. Telomere length, a key biomarker of cellular aging, naturally declines with age; however, malaria-associated inflammation appears to expedite this process. Telomere shortening can be counteracted by Telomerase, an enzyme whose activity is tightly regulated by human Telomerase reverse transcriptase (hTERT). Telomerase and hTERT contribute to genomic stability and cellular longevity, with hTERT expression modulated by IL-6 through activation of the Janus kinase signal transducer and activator of transcription (JAK-STAT) pathway. Despite this understanding, the relationship between telomerase activity, telomere length, IL-6 levels, hTERT expression, and malaria infection remains poorly understood. This review synthesizes current findings on IL-6-mediated inflammation and its potential impact on telomere length, telomerase activity, and hTERT expression. We examine studies exploring how persistent inflammation in malaria may drive cellular senescence, telomere dysfunction, and disease severity. Gaining knowledge of how IL-6 regulates Telomerase may help identify new biomarkers, therapeutic targets, and immune based interventions for malaria-induced immune dysregulation. Future research should focus on elucidating the precise molecular mechanisms linking inflammation to telomere dynamics and exploring strategies to mitigate immune cell senescence in malaria patients.Item EVALUATION OF SYNTHETIC FLAVONOID BASED COMPOUNDS AS INHIBITORS OF Plasmodium falciparum TRANSKETOLASE(Covenant University Ota, 2025-09) OROGUN, Yetunde Grace; Covenant University DissertationMalaria, primarily attributed to Plasmodium falciparum, remains a significant contributor to global mortality, with Africa experiencing the greatest burden, particularly in countries such as Nigeria, the Democratic Republic of Congo, and Mozambique. The rise in resistance to present therapies, including Artemisinin-based Combination Therapies (ACTs), underscores the urgent need for novel drug targets. Transketolase, a thiamine-dependent enzyme in the non-oxidative arm of the pentose phosphate pathway, is vital for parasite metabolism and structurally distinct from the human enzyme, making it a promising selective target. Twenty synthetic flavonoid-based compounds were evaluated as potential inhibitors of P. falciparum transketolase (PfTk). Molecular docking revealed strong binding affinities, while ADMET profiling showed that most compounds complied with Lipinski’s rule. Notably, Compounds 6, 7, 11, and 13 were predicted to be orally bioavailable with favorable pharmacokinetic and drug-likeness properties. The compounds were further tested in vitro against PfTk and human transketolase (hTk), with oxythiamine as the positive control, and cytotoxicity was assessed using hemolysis assays on human red blood cells. The results demonstrated that several compounds exhibited high potency and selective inhibition of PfTk with minimal activity on hTk. Among them, Compounds 6, 7, and 10 emerged as the most promising leads, combining high selectivity, oral bioavailability, and favorable safety margins. Additionally, Compounds 11 and 13, analogues of Compound 10, showed good drug-likeness and oral bioavailability, indicating potential for structural optimization. Hemolysis assays confirmed minimal red blood cell lysis across all compounds, supporting their safety. In conclusion, this study validates PfTk as a viable drug target and identifies Compounds 6, 7, and 10 as strong lead candidates, with Compounds 11 and 13 as promising analogues for further optimization and development of safe, effective antimalarial agents.Item EFFECTS OF INTERLEUKIN- 6 MEDIATED INFLAMMATION ON TELOMERASE EXPRESSION IN MALARIA PATIENTS(Covenant University Ota, 2025-09) FIAMITIA, Carrin; Covenant University DissertationMalaria remains a major global health burden that mostly affects young children in the African region, which has been associated with cellular aging and immune system exhaustion that is potentially mediated through telomere shortening and altered telomerase activity. The influence of malaria on the catalytic subunit hTERT, and how it modulates telomerase expression, in relation to the proinflammatory cytokines such as interleukin-6 (IL-6) and interferon-gamma (IFN-γ) is yet to be established. This study, therefore, aimed to explore the relationship between IL-6, IFN-γ levels, and hTERT gene expression in individuals with malaria infection. Ethical approval was obtained from the Covenant Health Research Ethics Committee (CHREC) before commencement of the study. A total of 50 malaria-infected samples were collected from ACE-Medicare and Covenant University Medical Center. Plasma generated from venous blood samples (5 ml) was separated by centrifugation, collected, and stored at –80 °C for subsequent cytokine analysis. Total RNA was extracted for cDNA synthesis and RT-qPCR-based quantification of hTERT expression. RNA concentration, integrity, and purity were analyzed using a Nanodrop spectrophotometer. A portion of the plasma (100 μl) was used for cytokine analysis using human IL-6 and IFN-γ using ELISA technique. Interleukin-6 levels (17.47 ± 25.11 pg/ml) were significantly higher (p<0.05) in the case compared to the control group (0.54 ± 0.46 pg/ml). The interferon gamma levels (117.74 ± 51.62 pg/ml) in the case group showed no significant difference (p>0.05) compared to the control group (104.50 ± 55.23 pg/ml). The Ct values of the hTERT gene expression were 33.38±4.48 in malaria patients in Nigeria, which is a possible standard range. For the first time, this study reports hTERT gene expression levels in Nigerian malaria patients and IL-6 as potential biomarkers for monitoring malaria progression, thereby providing a valuable tool for precision malaria treatment in NigeriaItem EFFECTS OF INTERLEUKIN- 6 MEDIATED INFLAMMATION ON TELOMERASE EXPRESSION IN MALARIA PATIENTS(Covenant University Ota, 2025-09) FIAMITIA, Carrin; Covenant University DissertationMalaria remains a major global health burden that mostly affects young children in the African region, which has been associated with cellular aging and immune system exhaustion that is potentially mediated through telomere shortening and altered telomerase activity. The influence of malaria on the catalytic subunit hTERT, and how it modulates telomerase expression, in relation to the proinflammatory cytokines such as interleukin-6 (IL-6) and interferon-gamma (IFN-γ) is yet to be established. This study, therefore, aimed to explore the relationship between IL-6, IFN-γ levels, and hTERT gene expression in individuals with malaria infection. Ethical approval was obtained from the Covenant Health Research Ethics Committee (CHREC) before commencement of the study. A total of 50 malaria-infected samples were collected from ACE-Medicare and Covenant University Medical Center. Plasma generated from venous blood samples (5 ml) was separated by centrifugation, collected, and stored at –80 °C for subsequent cytokine analysis. Total RNA was extracted for cDNA synthesis and RT-qPCR-based quantification of hTERT expression. RNA concentration, integrity, and purity were analyzed using a Nanodrop spectrophotometer. A portion of the plasma (100 μl) was used for cytokine analysis using human IL-6 and IFN-γ using ELISA technique. Interleukin-6 levels (17.47 ± 25.11 pg/ml) were significantly higher (p<0.05) in the case compared to the control group (0.54 ± 0.46 pg/ml). The interferon gamma levels (117.74 ± 51.62 pg/ml) in the case group showed no significant difference (p>0.05) compared to the control group (104.50 ± 55.23 pg/ml). The Ct values of the hTERT gene expression were 33.38±4.48 in malaria patients in Nigeria, which is a possible standard range. For the first time, this study reports hTERT gene expression levels in Nigerian malaria patients and IL-6 as potential biomarkers for monitoring malaria progression, thereby providing a valuable tool for precision malaria treatment in Nigeria.