2022
DOI: 10.3390/v14030605
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Multiscale Model of 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 o… Show more

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Cited by 14 publications
(9 citation statements)
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“…In general, scDisProcema provides a practical way for investigating dynamic complex biological systems. However, in the current state, it has not yet been possible for scDisProcema to characterize heterogeneity information in disease processes at a finer granularity, such as the behavior of individual cells and intercellular variation—which was considered of great importance by some researchers [57] . We believe this could be a good direction for our future study.…”
Section: Discussionmentioning
confidence: 99%
“…In general, scDisProcema provides a practical way for investigating dynamic complex biological systems. However, in the current state, it has not yet been possible for scDisProcema to characterize heterogeneity information in disease processes at a finer granularity, such as the behavior of individual cells and intercellular variation—which was considered of great importance by some researchers [57] . We believe this could be a good direction for our future study.…”
Section: Discussionmentioning
confidence: 99%
“…ABMs represent the behaviors and interactions of autonomous agents, such as cells, which are governed by literature-derived rules 15,21,22 . Agent-based modeling provides an excellent platform for studying complex cellular dynamics because they reveal how the interactions between individual cellular behaviors lead to emergent behaviors in the whole system.…”
Section: Methodsmentioning
confidence: 99%
“…CC3D provides additional applications of interest using SimService for integrative modeling and simulation. First, embedded models have become commonplace in multicellular simulation to describe subcellular and/or systems state dynamics, such as when modeling in vivo and in vitro viral infection, immune response and drug dosing ( Sego et al 2020 , Aponte-Serrano et al 2021 , Ferrari Gianlupi et al 2022 , Sego et al 2022 ) in CC3D using ordinary differential equation models specified in Antimony or the Systems Biology Markup Language and executed in libRoadRunner ( Smith et al 2009 , Somogyi et al 2015 , Keating et al 2020 ). While libRoadRunner supports launching multiple simulation instances from the same process, SimService enables providing the same capability for frameworks without such support such that, e.g.…”
Section: Applicationsmentioning
confidence: 99%
“…a medical digital twin). For example, the integration of libRoadRunner ( Somogyi et al 2015 ), Antimony ( Smith et al 2009 ) and MaBoSS ( Stoll et al 2017 ) in CompuCell3D ( Swat et al 2012 ) supports applications such as explicit multicellular spatial modeling in physiologically based pharmacokinetic—pharmacodynamic modeling of drug uptake, distribution and metabolism ( Sluka et al 2016 , Ferrari Gianlupi et al 2022 ). Vivarium provides an interface to build and execute integrated simulations using user-defined implementations and supported simulators ( Agmon et al 2022 ).…”
mentioning
confidence: 99%