Biology subjects

Nyarko, P.

Publications and source records attributed to Nyarko, P..

5 recordsLinked to original sources

bioRxiv2025

De novo assembly of complete Plasmodium falciparum isolate genomes using PacBio HiFi sequencing technology

Plasmodium falciparum possesses a highly structured genome with extensive sequence diversity concentrated in Variant Surface Antigen (VSA) families. These genes--var, rif, and stevor--play key roles in immune evasion and pathogenesis and are difficult to assemble using short-read sequencing technologies. Here, we applied PacBio HiFi long-read sequencing to generate high-quality de novo genome assemblies from 43 P. falciparum parasite cultures originating from community cases in The Gambia. Parasites were culture-adapted, cloned by limiting dilution where possible, and sequenced using high molecular weight DNA extracts. Assemblies from single-genotype lineages were constructed using hifiasm, producing complete chromosomal-length scaffolds with high base accuracy without requiring short-read polishing. We recovered full repertoires of var, rif, and stevor genes and classified them into known subgroups. Together, our results demonstrate that PacBio HiFi sequencing enables accurate assembly of complex P. falciparum genomes from natural infections. This work provides a valuable genomic resource for future studies of parasite evolution, transmission dynamics, and antigenic diversity, and suggests that VSA repertoires can serve as reliable proxies of genetic relatedness across infections.

genomics↗

bioRxiv2025

Moremi Bio Agent: Leveraging Agentic Large Language Model for the Discovery of Broad-Spectrum Antibiotics for Enterobacteriaceae

Antimicrobial resistance (AMR) is a pressing global health crisis, exacerbated by a stagnating antibiotic discovery pipeline and the emergence of multidrug-resistant pathogens such as Klebsiella pneumoniae. We hypothesize that dual-target strategies may offer a more robust means to overcome AMR by reducing the likelihood of resistance development compared to single-target approaches. In response, we leveraged Moremi Bio Agent, an agentic large language model (LLM) for the autonomous design, in silico validation, and prioritization of broad-spectrum antibiotics targeting Enterobacteriaceae. Using our proposed dual-target strategy, we generated and evaluated 1,002 candidate molecules predicted to simultaneously inhibit the FabI enzyme and the AcrAB-TolC efflux pump--two key resistance mechanisms in Gram-negative bacteria. Our fully autonomous pipeline integrated compound generation, molecular docking, pharmacodynamics/pharmacokinetic predictions & toxicity profiling, and molecule-ranking based on ADMET and drug-likeness properties. Out of 1,002 molecules generated, 774 passed preliminary ADMET benchmarks, with majority of the 60 top-performing candidates (score[≥] 0.8) showing favorable drug-likeness, minimal toxicity. 391 of the compounds exhibited moderate binding interaction to both targets. This study demonstrates the feasibility of AI-driven antibiotic discovery and lays the foundation for future experimental validation to address AMR.

biochemistry↗

bioRxiv2025

Moremi Bio Agent: Application of A Foundation Model and End-to-End Automation in the Design and Validation of Monoclonal Antibodies Targeting Plasmodium falciparum Invasion Complex

Malaria remains a significant global health challenge, with Plasmodium falciparum responsible for the majority of severe cases and fatalities. Targeting the parasites invasion mechanisms offers a promising therapeutic strategy. In this study, we leveraged a novel agentic foundational model, Moremi Bio Agent, to design monoclonal antibodies targeting the AMA1-RON2 complex, a critical component in the parasites invasion of human red blood cells. Using advanced structural modeling, we generated 999 antibodies, which were evaluated for binding affinity, structural integrity, and physicochemical properties. Binding affinity analysis using PRODIGY identified 864 antibodies with successful target interactions, exhibiting binding free energies ({Delta}G) ranging from -116.8 kcal/mol to -5.6 kcal/mol. The strongest candidates demonstrated exceptionally tight binding, with dissociation constants (Kd) in the femtomolar to attomolar range, indicative of highly stable interactions. Additionally, structural validation confirmed that the antibodies were thermodynamically stable with robust fold reliability, essential for functional efficacy. Epitope mapping revealed highly conserved regions within the target complex, enhancing the likelihood of cross-strain efficacy. Glycosylation analysis identified key sites that could improve antibody stability and immune recognition, while BLAST comparison with known therapeutic antibodies demonstrated significant homology, underscoring their potential for clinical development. This study highlights the power of generative AI-driven computational pipelines in antibody discovery, providing a scalable and cost-effective framework for therapeutic development. The findings establish a foundation for experimental validation and optimization, with the potential to advance novel interventions against malaria and other infectious diseases.

synthetic biology↗

bioRxiv2023

RNA polymerase III is involved in regulating Plasmodium falciparum virulence

While often undetected and untreated, persistent seasonal asymptomatic malaria infections remain a global public health problem. Despite the presence of parasites in the peripheral blood, no symptoms develop. Disease severity is correlated with the levels of infected red blood cells (iRBCs) adhering within blood vessels. Changes in iRBC adhesion capacity have been linked to seasonal asymptomatic malaria infections, however how this is occurring is still unknown. Here we present evidence that RNA polymerase III (RNA Pol III) transcription in Plasmodium falciparum is downregulated in field isolates obtained from asymptomatic individuals during the dry season. Through experiments with in vitro cultured parasites, we have uncovered an RNA Pol III-dependent mechanism that controls pathogen proliferation and expression of a major virulence factor in response to external stimuli. Our findings establish a connection between P. falciparum cytoadhesion and a non-coding RNA family transcribed by Pol III. Additionally, we have identified P. falciparum Maf1 as a pivotal regulator of Pol III transcription, both for maintaining cellular homeostasis and responding adaptively to external signals. These results introduce a novel perspective that contributes to our understanding of P. falciparum virulence. Furthermore, they establish a connection between this regulatory process and the occurrence of seasonal asymptomatic malaria infections.

microbiology↗

bioRxiv2021

In vitro analysis of the effects of acetaminophen, ibuprofen and aspirin on motility of female adult Onchocerca volvulus worms

In view of the very ambitious global timelines for elimination of onchocerciasis in 2030, the search for alternative antifilarials cannot depend on drug development from scratch, and repurposed drugs offer cheaper and faster alternatives. Previous studies had demonstrated the presence and potential expression of amidase, an enzyme that can be targeted by repurposed analgesics, in Onchocerca volvulus worms. The aim of this study was to determine the effects of acetaminophen, ibuprofen and aspirin on the motility of adult O. volvulus worms. In total, thirty (30) female O. volvulus worms were exposed to acetaminophen, ibuprofen and aspirin in concentrations of either 5mg/ml, 2.5mg/ml, 1.25mg/ml or 0.63mg/ml control in duplicates. Worm motility was observed and recorded using the WormAssay software and a darkfield imaging apparatus starting on day 2 of incubation and ending on day 8. Acetaminophen, ibuprofen and aspirin inhibited O. volvulus motility by 2-fold compared to control in the first 24 hours of drug exposure. However, an extended exposure of the worms to these test drugs rather improved the motility of the worms. The study has demonstrated that a 24-hour exposure of O. volvulus worms to the analgesic drugs studied, results in significant inhibition in worm motility compared with the control group, but extended duration of exposure led to an enhancement in motility of the previously immobile worms. This finding supports the idea that aspirin and ibuprofen may have some longevity enhancing properties. Further research on the utility of these analgesics as possible anti-filarial drugs is thus warranted.

microbiology↗