Biology subjects

Mercer, L.

Publications and source records attributed to Mercer, L..

2 recordsLinked to original sources

bioRxiv2020

Repurposing Pyramax for the Treatment of Ebola Virus Disease: Additivity of the Lysosomotropic Pyronaridine and Non-Lysosomotropic Artesunate

We have recently identified three molecules (tilorone, quinacrine and pyronaridine tetraphosphate) which all demonstrated efficacy in the mouse model of infection with mouse-adapted Ebola virus (EBOV) model of disease and had similar in vitro inhibition of an Ebola pseudovirus (VSV-EBOV-GP), suggesting they interfere with viral entry. Using a machine learning model to predict lysosomotropism these compounds were evaluated for their ability to inhibit via a lysosomotropic mechanism in vitro. We now demonstrate in vitro that pyronaridine tetraphosphate is an inhibitor of Lysotracker accumulation in lysosomes (IC50 = 0.56 M). Further, we evaluated synergy between pyronaridine and artesunate (Pyramax(R)), which are used in combination to treat malaria. Artesunate was not found to have lysosomotropic activity in vitro and the combination effect on EBOV inhibition was shown to be additive. Pyramax(R) may represent a unique example of the repurposing of a combination product for another disease.

pharmacology and toxicology↗

bioRxiv2019

Evidence of the Cost-Efficiency of Scale as seen in Polio Vaccination and Surveillance Costs

This analysis examined how polio program costs vary with scale for vaccination and disease surveillance, based on historical budget data published by the Global Polio Eradication Initiative (GPEI) from 2005 to 2018. We applied a linear mixed effects regression model in order to understand the cost structure of the historical GPEI budgets, with the goal that lessons learned from polio may be extended to other global disease elimination programs. Our findings demonstrate that there are economies of scale for vaccine delivery operations and for disease surveillance, which means that larger programs can leverage fixed costs and achieve better cost-efficiency as they scale. This finding should enable decision makers to create more reliable budgets, which support fundraising and optimal resource allocation. They also provide insight into how cost effectiveness changes as programs scale up during progressive disease control and elimination, as well as what level of resources are needed to sustain a program that is scaling back post-eradication and through to certification.

epidemiology↗