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Gianlupi2022 - Antiviral Timing, Potency, and Heterogeneity Effects on an Epithelial Tissue Patch Infected by SARS-CoV-2

ABSTRACT: We extend our established agent-based multiscale computational model of infection of lung tissue by SARS-CoV-2 to include pharmacokinetic and pharmacodynamic models of remdesivir. We model remdesivir treatment for COVID-19; however, our methods are general to other viral infections and antiviral therapies. We investigate the effects of drug potency, drug dosing frequency, treatment initiation delay, antiviral half-life, and variability in cellular uptake and metabolism of remdesivir and its active metabolite on treatment outcomes in a simulated patch of infected epithelial tissue. Non-spatial deterministic population models which treat all cells of a given class as identical can clarify how treatment dosage and timing influence treatment efficacy. However, they do not reveal how cell-to-cell variability affects treatment outcomes. Our simulations suggest that for a given treatment regime, including cell-to-cell variation in drug uptake, permeability and metabolism increase the likelihood of uncontrolled infection as the cells with the lowest internal levels of antiviral act as super-spreaders within the tissue. The model predicts substantial variability in infection outcomes between similar tissue patches for different treatment options. In models with cellular metabolic variability, antiviral doses have to be increased significantly (>50% depending on simulation parameters) to achieve the same treatment results as with the homogeneous cellular metabolism.

SUBMITTER: Juliano Ferrari Gianlupi

PROVIDER: MODEL2212160001 | BioModels | 2022-12-30

REPOSITORIES: BioModels

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			Action	DRS
	MODEL2212160001?filename=DrugDosingInputs.py	Other
	MODEL2212160001?filename=DrugDosingModelSteppable.py	Other
	MODEL2212160001?filename=Model-Antiviral-Heterogeneity-Tissue-Infected-SARS-2.zip	Other
	MODEL2212160001?filename=ViralInfectionVTM.cc3d	Other
	MODEL2212160001?filename=ViralInfectionVTM.py	Other

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Gianlupi2022 - Antiviral Timing, Potency, and Heterogeneity Effects on an Epithelial Tissue Patch Infected by SARS-CoV-2

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