Browsing by Author "Adebiyi, Ezekiel"

Now showing 1 - 4 of 4

Exome sequencing in Nigerian children with early-onset epilepsy syndromes
(Epilepsia Open, 2024-10-31) Ademuwagun, Ibitayo Abigail; Adam, Yagoub; Rotimi, Solomon Oladapo; Syrbe, Steffen; Radtke, Maximilian; Hentschel, Julia; Lemke, Johannes R.; Adebiyi, Ezekiel
Objective: Nigeria, along with other Sub-Saharan African countries, bears the highest burden of epilepsy worldwide. This high prevalence is attributed to a combination of factors, including a significant incidence of infectious diseases, perinatal complications, and genetic etiologies. Genetic testing is rarely available and is not typically included in the routine diagnostic work-up for individuals with infantile and childhood epilepsy syndromes in these regions. Exome sequencing (ES) offers a diagnostic yield of 24%–62%, but these figures primarily reflect data from high-income countries (HICs) and may not be applicable to low-and middle-income countries (LMICs). In this study, we employed ES to investigate the genetic basis of early-onset epilepsy in 22 affected children from Nigeria. Methods: The study involved sampling of patients diagnosed with early-onset epilepsy syndromes at the Lagos State University Teaching Hospital (LASUTH) Neurology clinic. Venous blood samples were collected, and genomic DNA was isolated and purified. Molecular analysis included DNA fragmentation, ligation, target enrichment, library preparation, and whole-exome sequencing. Computational analysis involved variant calling, curation, and classification using specialized tools and databases. Results: Pathogenic variants were identified in 6 out of 22 individuals, equaling a diagnostic yield of 27.3% and comprising variants in BPTF, NAA15, SCN1A, TUBA1A and twice in CACNA1A. Significance: In this study, we present the first exome study on early-onset epilepsy syndromes from West Africa, facilitated by a Nigerian-German research collaboration. Our findings reveal a genetic diagnostic yield comparable to that of HICs. The integration of genomic medicine into epilepsy management in Nigeria holds promising prospects for improving patient care and reducing mortality rates
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, Ezekiel
Plasmodium 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.
The Importance of Murine Models and Their Resultant In Vivo Pharmacokinetics, Safety, and Efficacy Assessments for Antimalarial Drug Discovery
(Preprints, 2026) Adebayo, Glory; Ayanda, Opeyemi I.; Rottmann, Matthias; Ajibaye, Olusola; Oduselu, Gbolahan; Mulindwa, Julius; Ajani, Olayinka O.; Aina, Oluwagbemig; Mäser, Pascal; Adebiyi, Ezekiel
New chemical entities are consistently being investigated in antimalarial drug discovery and they require animal models for toxicity and efficacy testing. Murine models in searching for novel antimalarial drugs are inevitable because they show unique similarities to human physiology during malaria pathogenesis. Therefore, they provide a preclinical basis (following in vitro assessments of newly identified lead compounds) for further assessment in the drug development pipeline. Specific mouse strains, non-humanized and humanized, have successfully been infected with rodent Plasmodium species and the human Plasmodium falciparum respectively. Infected mice provide a platform for the assessment of treatment options being sought. In vivo pharmacokinetic evaluations are necessary when determining the fate of new lead compounds in addition to the efficacy assessment of these chemical entities. This review highlights specific murine models important for antimalarial drug discovery and their resultant critical in vivo pharmacokinetic, safety, and efficacy assessments necessary for making appropriate choices of lead compounds
The Importance of Murine Models in Determining In Vivo Pharmacokinetics, Safety, and Efficacy in Antimalarial Drug Discovery
(Pharmaceuticals (MDPI), 2025) Adebayo, Glory; Ayanda, Opeyemi I.; Rottmann, Matthias; Ajibaye, Olusola S.; Oduselu, Gbolahan; Oduselu, Gbolahan; Mulindwa, Julius; Ajani, Olayinka O.; Aina, Oluwagbemiga; Mäser, Pascal; Adebiyi, Ezekiel
New chemical entities are constantly being investigated towards antimalarial drug discovery, and they require animal models for toxicity and efficacy testing. Murine models show physiological similarities to humans and are therefore indispensable in the search for novel antimalarial drugs. They provide a preclinical basis (following in vitro assessments of newly identified lead compounds) for further assessment in the drug development pipeline. Specific mouse strains, non-humanized and humanized, have successfully been infected with rodent Plasmodium species and the human Plasmodium species, respectively. Infected mice provide a platform for the assessment of treatment options being sought. In vivo pharmacokinetic evaluations are necessary when determining the fate of potential antimalarials in addition to the efficacy assessment of these chemical entities. This review describes the role of murine models in the drug development pipeline. It also explains some in vivo pharmacokinetic, safety, and efficacy parameters necessary for making appropriate choices of lead compounds in antimalarial drug discovery. Despite the advantages of murine models in antimalarial drug discovery, certain limitations are also highlighted.