Development of a novel mathematical model that explains SARS-CoV-2 infection dynamics in Caco-2 cells

Mathematical modeling is widely used to study within-host viral dynamics. However, to the best of our knowledge, for the case of SARS-CoV-2 such analyses were mainly conducted with the use of viral load data and for the wild type (WT) variant of the virus. In addition, only few studies analyzed mode...

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Main Authors: Vladimir Staroverov, Stepan Nersisyan, Alexei Galatenko, Dmitriy Alekseev, Sofya Lukashevich, Fedor Polyakov, Nikita Anisimov, Alexander Tonevitsky
Format: Article
Language:English
Published: PeerJ Inc. 2023-02-01
Series:PeerJ
Subjects:
Online Access:https://peerj.com/articles/14828.pdf
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author Vladimir Staroverov
Stepan Nersisyan
Alexei Galatenko
Dmitriy Alekseev
Sofya Lukashevich
Fedor Polyakov
Nikita Anisimov
Alexander Tonevitsky
author_facet Vladimir Staroverov
Stepan Nersisyan
Alexei Galatenko
Dmitriy Alekseev
Sofya Lukashevich
Fedor Polyakov
Nikita Anisimov
Alexander Tonevitsky
author_sort Vladimir Staroverov
collection DOAJ
description Mathematical modeling is widely used to study within-host viral dynamics. However, to the best of our knowledge, for the case of SARS-CoV-2 such analyses were mainly conducted with the use of viral load data and for the wild type (WT) variant of the virus. In addition, only few studies analyzed models for in vitro data, which are less noisy and more reproducible. In this work we collected multiple data types for SARS-CoV-2-infected Caco-2 cell lines, including infectious virus titers, measurements of intracellular viral RNA, cell viability data and percentage of infected cells for the WT and Delta variants. We showed that standard models cannot explain some key observations given the absence of cytopathic effect in human cell lines. We propose a novel mathematical model for in vitro SARS-CoV-2 dynamics, which included explicit modeling of intracellular events such as exhaustion of cellular resources required for virus production. The model also explicitly considers innate immune response. The proposed model accurately explained experimental data. Attenuated replication of the Delta variant in Caco-2 cells could be explained by our model on the basis of just two parameters: decreased cell entry rate and increased cytokine production rate.
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spelling doaj.art-07cac33da9d1411a8a20aa87e41e48ed2023-12-03T10:00:12ZengPeerJ Inc.PeerJ2167-83592023-02-0111e1482810.7717/peerj.14828Development of a novel mathematical model that explains SARS-CoV-2 infection dynamics in Caco-2 cellsVladimir Staroverov0Stepan Nersisyan1Alexei Galatenko2Dmitriy Alekseev3Sofya Lukashevich4Fedor Polyakov5Nikita Anisimov6Alexander Tonevitsky7Faculty of Biology and Biotechnology, HSE University, Moscow, RussiaFaculty of Biology and Biotechnology, HSE University, Moscow, RussiaFaculty of Biology and Biotechnology, HSE University, Moscow, RussiaFaculty of Biology and Biotechnology, HSE University, Moscow, RussiaFaculty of Biology and Biotechnology, HSE University, Moscow, RussiaFaculty of Biology and Biotechnology, HSE University, Moscow, RussiaFaculty of Biology and Biotechnology, HSE University, Moscow, RussiaFaculty of Biology and Biotechnology, HSE University, Moscow, RussiaMathematical modeling is widely used to study within-host viral dynamics. However, to the best of our knowledge, for the case of SARS-CoV-2 such analyses were mainly conducted with the use of viral load data and for the wild type (WT) variant of the virus. In addition, only few studies analyzed models for in vitro data, which are less noisy and more reproducible. In this work we collected multiple data types for SARS-CoV-2-infected Caco-2 cell lines, including infectious virus titers, measurements of intracellular viral RNA, cell viability data and percentage of infected cells for the WT and Delta variants. We showed that standard models cannot explain some key observations given the absence of cytopathic effect in human cell lines. We propose a novel mathematical model for in vitro SARS-CoV-2 dynamics, which included explicit modeling of intracellular events such as exhaustion of cellular resources required for virus production. The model also explicitly considers innate immune response. The proposed model accurately explained experimental data. Attenuated replication of the Delta variant in Caco-2 cells could be explained by our model on the basis of just two parameters: decreased cell entry rate and increased cytokine production rate.https://peerj.com/articles/14828.pdfMathematical modelSARS-CoV-2COVID-19Caco-2
spellingShingle Vladimir Staroverov
Stepan Nersisyan
Alexei Galatenko
Dmitriy Alekseev
Sofya Lukashevich
Fedor Polyakov
Nikita Anisimov
Alexander Tonevitsky
Development of a novel mathematical model that explains SARS-CoV-2 infection dynamics in Caco-2 cells
PeerJ
Mathematical model
SARS-CoV-2
COVID-19
Caco-2
title Development of a novel mathematical model that explains SARS-CoV-2 infection dynamics in Caco-2 cells
title_full Development of a novel mathematical model that explains SARS-CoV-2 infection dynamics in Caco-2 cells
title_fullStr Development of a novel mathematical model that explains SARS-CoV-2 infection dynamics in Caco-2 cells
title_full_unstemmed Development of a novel mathematical model that explains SARS-CoV-2 infection dynamics in Caco-2 cells
title_short Development of a novel mathematical model that explains SARS-CoV-2 infection dynamics in Caco-2 cells
title_sort development of a novel mathematical model that explains sars cov 2 infection dynamics in caco 2 cells
topic Mathematical model
SARS-CoV-2
COVID-19
Caco-2
url https://peerj.com/articles/14828.pdf
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