College of Science and Technology

Permanent URI for this communityhttp://itsupport.cu.edu.ng:4000/handle/123456789/28738

Welcome to the community of research works in Science and Technology

Browse

Subject: search.filters.subject.malaria

Search Results

Now showing 1 - 6 of 6
  • No Thumbnail Available
    Item
    Ex Vivo Molecular Studies and In Silico Small Molecule Inhibition of Plasmodium falciparum Bromodomain Protein 1
    (Drugs Drug Candidates, 2025-06-22) Oladejo, David O.; Dokunmu, Titilope M.; Oduselu, Gbolahan O.; Oladejo, Daniel O.; Ogunlana, Olubanke O.; Iweala, Emeka E. J.
    Background: Malaria remains a significant global health burden, particularly in sub- Saharan Africa, accounting for high rates of illness and death. The growing resistance to frontline antimalarial therapies underscores the urgent need for novel drug targets and therapeutics. Bromodomain-containing proteins, which regulate gene expression through chromatin remodeling, have gained attention as potential targets. Plasmodium falciparum bromodomain protein 1 (Pf BDP1), a 55 kDa nuclear protein, plays a key role in recognizing acetylated lysine residues and facilitating transcription during parasite development. Methods: This study investigated ex vivo PfBDP1 gene mutations and identified potential small molecule inhibitors using computational approaches. Malariapositive blood samples were collected. Genomic DNA was extracted, assessed for quality, and amplified using Pf BDP1-specific primers. DNA sequencing and alignment were performed to determine single-nucleotide polymorphism (SNP). Structural modeling used the PfBDP1 crystal structure (PDB ID: 7M97), and active site identification was conducted using CASTp 3.0. Virtual screening and pharmacophore modeling were performed using Pharmit and AutoDock Vina, followed by ADME/toxicity evaluations with SwissADME, OSIRIS, and Discovery Studio. GROMACS was used for 100 ns molecular dynamics simulations. Results: The malaria prevalence rate stood at 12.24%, and the sample size was 165. Sequencing results revealed conserved PfBDP1 gene sequences compared to the 3D7 reference strain. Virtual screening identified nine lead compounds with binding affinities ranging from −9.8 to −10.7 kcal/mol. Of these, CHEMBL2216838 had a binding affinity of −9.9 kcal/mol, with post-screening predictions of favorable drug-likeness (8.60), a high drug score (0.78), superior pharmacokinetics, and a low toxicity profile compared to chloroquine. Molecular dynamics simulations confirmed its stable interaction within the PfBDP1 active site. Conclusions: Overall, this study makes a significant contribution to the ongoing search for novel antimalarial drug targets by providing both molecular and computational evidence for PfBDP1 as a promising therapeutic target. The prediction of CHEMBL2216838 as a lead compound with favorable binding affinity, drug-likeness, and safety profile, surpassing those of existing drugs like chloroquine, sets the stage for preclinical validation and further structure-based drug design efforts. These findings are supported by prior experimental evidence showing significant parasite inhibition and gene suppression capability of predicted hits.
  • No Thumbnail Available
    Item
    Knowledge, practices, and perceptions towards malaria prevention and control among Residents of Canaanland and surrounding areas in Ota, Ogun State, Nigeria: a cross-sectional study
    (Frontiers in Tropical Diseases, 2025-10-13) Wakai, Theophilus N.; Fiamitia, Carrin; Kintung, Irrinus; Johngwe, Mac; Chinedu, Shalom; Afolabi, Israel S.
  • No Thumbnail Available
    Item
    Plasmodium telomere maintenance: uncovering the Achilles’ heel for novel antimalarials
    (Frontiers in Cellular and Infection Microbiology, 2025-09) Wakai, Theophilus N.; Anzaku, Dorathy O.; Afolabi, Israel S.
    This review examines the potential of disrupting telomere maintenance in Plasmodium as a novel antimalarial strategy. Telomeres are repetitive DNA– protein structures located at chromosome termini, where they preserve genome stability and protect against degradation. Telomere maintenance is crucial for rapid growth, genome integrity, and immune evasion in Plasmodium parasites. Unlike humans, Plasmodium maintains continuous telomerase activity and uses unique telomere-binding proteins across its lifecycle. These features drive parasite virulence and antigenic variation. Emerging evidence suggests that Plasmodium telomeres harbor G-quadruplex (G4) DNA structures, which help stabilize telomeres during replication and may be good targets for small molecules to disrupt their function. Additionally, the parasite depends heavily on its telomerase catalytic subunit, PfTERT, for survival. Inhibiting PfTERT has shown promising results in blocking telomere elongation and impairing replication. Targeting this parasite-specific telomere–telomerase axis may offer a strategic means to destabilize chromosomes, weaken immune evasion, and limit parasite survival, making it a promising antimalarial approach. However, researchers must consider the risks of off-target effects in future drug designs. Though current studies are limited and remain inconclusive, we suggest that future research should investigate combining telomere-directed therapies with existing antimalarials to help overcome resistance and improve treatment outcomes. Herein, we review advances in understanding Plasmodium telomere biology, highlighting its distinct structures, critical telomereassociated proteins, and roles in pathogenesis. We further explore how selective targeting could exploit an Achilles’ heel in parasite survival, offering fresh possibilities for next-generation, parasite-specific malaria therapies.
  • No Thumbnail Available
    Item
    Critical Understanding of the Influence of Cellular Aging Biomarkers on Host–Parasite Relationships Serving as a Key Platform for Malaria Eradication
    (2025) Anzaku, Dorathy Olo; Afolabi, Israel Sunmola
    Plasmodium parasites are the causative agents of malaria and can infect humans and other vertebrates, impacting socioeconomic development and causing significant health issues globally. Plasmodium falciparum causes the most severe type of infection, which can lead to chronic morbidity and other severe complications like anemia and cerebral malaria. The onset of infection is marked by the injection of sporozoites into the skin through the bite of a female Anopheles mosquito. This triggers a cascade of reactions elicited both by the host immune system in response to infection and by the parasite in a bid to evade the host immune system, survive, and replicate. The dynamics of this host–parasite relationship have prompted extensive research in an attempt to understand and exploit it in the fight against malaria. Thus, understanding the temporal and spatial dimensions of adaptation in host–parasite relationships is critical for forecasting parasite evolution and spread within and between host populations. One such relationship is the complex interplay between malaria and cellular aging processes. Understanding this dynamic will provide novel insights into the pathophysiology of the disease. This comprehensive review takes us on that journey by providing an overview of the interaction between the Plasmodium parasite and its host and the interplay between infection mechanisms, host immune response, and parasite evasion strategies, narrowing it down to how it affects cellular aging biomarkers and howthis can be explored as a platform in the fight against the disease
  • No Thumbnail Available
    Item
    Plasmodium falciparum Transketolase as a Drug Target in Malaria: A Review of Current Research and Future Perspectives
    (Journal of Science and Technology, Research Vol. 7, Special Issue: Landmark University International Conference, 2025) Orogun, Yetunde; Fadare, Olatomide; Bajepade, Tobilola; Raimi, Olawale; Ogunlana, Olubanke
    Malaria is a severe infectious disease caused by Plasmodium species, primarily Plasmodium falciparum, which accounts for the most deaths globally. Africa bears the heaviest malaria burden, with countries like Nigeria, Congo, and Mozambique contributing to a significant percentage of global cases. It is transmitted through the bite of an infected female Anopheles mosquito. The fight against malaria has been challenged by the emergence of resistance to most antimalarial drugs, including Artemisinin-based Combination Therapies (ACTs). This highlights the urgent need for novel drug targets. Transketolase (Tk), a key enzyme in the pentose phosphate pathway (PPP) non-oxidative branch, plays a vital role in cellular metabolism and has been identified to support parasite survival. Plasmodium falciparum transketolase (PfTk) has been identified as an emerging drug target due to its essential role in the parasite's metabolism and low structural homology with human transketolase (HTk). This review aims to provide an overview of PfTk as a potential anti-malarial drug target and to highlight the key research direction for future drug development. It examines the current research on PfTk as a therapeutic target, focusing on its biochemical properties, structural and functional characteristics, and potential inhibitors' development as a therapeutic strategy while exploring future perspectives.
  • No Thumbnail Available
    Item
    SINGLE NUCLEOTIDE POLYMORPHISMS OF Pfdhfr RESISTANCE GENE AMONG SYMPTOMATIC PATIENTS’ ISOLATES FROM SELECTED HOSPITALS IN IFO LGA, OGUN STATE
    (Covenant University Ota, 2025-10) SULE, Queen Elizabeth; Covenant University Dissertation
    Malaria remains a primary universal health concern, particularly in endemic areas where drug resistance poses a serious threat to the effectiveness of key treatment and prevention strategies. Sulfadoxine-pyrimethamine (SP), commonly used for malaria prophylaxis, is increasingly compromised by resistance associated with mutations in the Plasmodium falciparum dihydrofolate reductase (Pfdhfr) gene. This study aimed to assess the prevalence of P. falciparum infection and identify the single-nucleotide polymorphisms (SNPs) in the Pfdhfr resistance gene among symptomatic patients in Ifo Local Government Area, Ogun State, Nigeria. Five hundred patients with severe P. falciparum infection were recruited, and demographic data were recorded. Blood samples were analysed for P. falciparum stages and parasitemia levels using microscopy. DNA was extracted from samples with high parasitemia and genotyped for Pfdhfr mutations using PCR, followed by visualisation on 1% agarose gel electrophoresis. Microscopy confirmed P. falciparum malaria in 300 patients (60%). A significantly higher prevalence (71.05%) was recorded in the 0–4 years’ age group, while males accounted for 64.31% of cases (p < 0.05). Parasitemia levels (greater than 200 parasites/100 μL) were more pronounced in males than in females, and were highest among individuals aged 0–4 years. Among the 10.67% Pfdhfr genotypes identified, males exhibited a higher frequency (6.0%) than females. The overall prevalence of pfdhfr SNPs in N51I, C59R, S108, and I64L was (96%), (96%), (100%), and (0%), respectively. tripple mutant halotype (N51I+ C59R+S108), prevance was 92%. Males have a higher mutation rate (60%) than females (40%). The overall prevalence of pfdhfr SNPs in N51I, C59R, S108, and I164L was (96%), (96%), (100%), and (0%), respectively. tripple mutant halotype (N51I+ C59R+S108), prevance was 92%. Males have a higher mutation rate (60%) than females (40%). Also, individuals aged 0-4 years (20%) and 15-20 years (20%) show higher SNPs than the other age groups. The study highlights a high prevalence of P. falciparum and emerging Pfdhfr resistance mutations, emphasising the need for continuous surveillance and targeted interventions in malaria-endemic regions, such as Ifo LGA, Nigeria.