Biology subjects

Nyarko, P.

Publications and source records attributed to Nyarko, P..

3 recordsLinked to original sources

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↗