Evidence map›Paper›PMID 35337012›Full record

ArticleViruses2022

Multiscale Model of Antiviral Timing, Potency, and Heterogeneity Effects on an Epithelial Tissue Patch Infected by SARS-CoV-2.

Juliano Ferrari Gianlupi, Tarunendu Mapder, T J Sego, James P Sluka, Sara K Quinney, Morgan Craig, Robert E Stratford, James A Glazier

Open access · goldAbstract read
In one paragraph

Article in Viruses, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.9field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 21 citations in OpenAlex.

  1. Spatially structured models of viral dynamics: a scoping review.Microbiology and molecular biology reviews : MMBR · 2025
    Article
  2. Systems Virology at Scale.Current opinion in systems biology · 2025
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 2 countries.

Juliano Ferrari GianlupiDepartment of Intelligent Systems Engineering and Biocomplexity Institute, Indiana University, 2425 N Milo B Sampson Ln, Bloomington, IN 47408, USA.ORCID 0000-0002-1305-146X
Tarunendu MapderDivision of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, 950 W Walnut Street, Indianapolis, IN 46202, USA.ORCID 0000-0002-1630-0716
T J SegoDepartment of Intelligent Systems Engineering and Biocomplexity Institute, Indiana University, 2425 N Milo B Sampson Ln, Bloomington, IN 47408, USA.
James P SlukaDepartment of Intelligent Systems Engineering and Biocomplexity Institute, Indiana University, 2425 N Milo B Sampson Ln, Bloomington, IN 47408, USA.ORCID 0000-0002-5901-1404
Sara K QuinneyDivision of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, 950 W Walnut Street, Indianapolis, IN 46202, USA.
Morgan CraigSainte-Justine University Hospital Research Centre and Department of Mathematics and Statistics, Université de Montréal, Montreal, QC H3T 1J4, Canada.ORCID 0000-0003-4852-4770
Robert E StratfordDivision of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, 950 W Walnut Street, Indianapolis, IN 46202, USA.
James A GlazierDepartment of Intelligent Systems Engineering and Biocomplexity Institute, Indiana University, 2425 N Milo B Sampson Ln, Bloomington, IN 47408, USA.ORCID 0000-0003-3634-190X
Indiana University Bloomington · USIndiana University School of MedicineUniversité de Montréal · CA

Funding

Quality Assurance and Quality Control Project Management: Improving Submissions and Study Conduct in the Human Subjects Research Prior Approval ProcessUL1TR002529 · NCATS · INDIANA UNIVERSITY INDIANAPOLIS · PI MOE, SHARON M, WIEHE, SARAH ELIZABETH · 2018 to 2022
$27.2M
Competitive Renewal of Development, Improvement and Extension of the Tissue Simulation Environment - CompuCell3DR01GM122424 · NIGMS · TRUSTEES OF INDIANA UNIVERSITY · PI GLAZIER, JAMES ALEXANDER · 2017 to 2020
$1.7M
Dissemination of libRoadRunner and CompuCell3DU24EB028887 · NIBIB · UNIVERSITY OF WASHINGTON · PI GLAZIER, JAMES ALEXANDER, SAURO, HERBERT M. · 2019 to 2023
$1.5M
National Science Foundation NSF 1720625Natural Sciences and Engineering Research Council NSERC ALLRP 554923 - 20Natural Sciences and Engineering Research Council RGPIN-2018-04546NCATS NIH HHS UL1 TR002529NIBIB NIH HHS U24 EB028887NIGMS NIH HHS R01 GM122424NIH HHS U24 EB028887, R01GM122424, UL1TR002529
6 · The paper itself

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.

Indexed as

Antiviral AgentsCOVID-19 Drug TreatmentEpitheliumHumansSARS-CoV-2Virus ReplicationAntiviral Agentsagent-based modelantiviral therapymPBPKmultiscale modelremdesivirSARS-CoV-2tissue modelvirtual tissue simulation

Identifiers

PMID35337012
PMCPMC8953050
OpenAlexW4220683058

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.