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Mathematical modeling of SARS-CoV-2 viral dynamics and treatment with monoclonal antibodies

The novel coronavirus (SARS-CoV-2) affects primarily the respiratory tract, and if left unchecked can cause a spectrum of pathological manifestations such as pneumonia, acute respiratory distress syndrome, myocardial injury, thromboembolism, and acute kidney injury. Medication strategies have involv...

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Autores principales: Kareva, Irina, Zutshi, Anup, Madrasi, Kumpal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: , IFAC (International Federation of Automatic Control) Hosting by Elsevier Ltd. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9903140/
http://dx.doi.org/10.1016/j.ifacol.2023.01.038
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author Kareva, Irina
Zutshi, Anup
Madrasi, Kumpal
author_facet Kareva, Irina
Zutshi, Anup
Madrasi, Kumpal
author_sort Kareva, Irina
collection PubMed
description The novel coronavirus (SARS-CoV-2) affects primarily the respiratory tract, and if left unchecked can cause a spectrum of pathological manifestations such as pneumonia, acute respiratory distress syndrome, myocardial injury, thromboembolism, and acute kidney injury. Medication strategies have involved minimizing the spread of the virus through antiviral medications (monoclonal antibodies or nucleotide reverse transcriptase inhibitors). Here, we develop a mathematical model that simulates viral dynamics in an untreated individual, and the evaluate the impact that a monoclonal antibody can have on slowing viral replication. Drug pharmacokinetics (PK) was informed by a typical two-compartment PK model with parameters typical of a monoclonal antibody, with a third compartment for the lung included as the drug site of action. The viral dynamics were captured using a simplified model describing uninfected target cells, infected target cells, and viral load in the body. The mechanism of action of the simulated antiviral is based on binding to the virus, thereby preventing it from infecting healthy cells. The model is used to project dosages needed to prevent severe disease under a variety of simulated conditions and subject to realistic constraints. The proposed model can capture a variety of scenarios of longitudinal viral dynamics and assess the impact of antiviral therapy on disease severity and duration. The described approach can be easily adapted to rapidly assess the dosages needed to affect duration and outcome of other viral infections and can serve as part of a fast and efficient scientific and modeling response strategy in the future as needed
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spelling pubmed-99031402023-02-07 Mathematical modeling of SARS-CoV-2 viral dynamics and treatment with monoclonal antibodies Kareva, Irina Zutshi, Anup Madrasi, Kumpal IFAC-PapersOnLine Article The novel coronavirus (SARS-CoV-2) affects primarily the respiratory tract, and if left unchecked can cause a spectrum of pathological manifestations such as pneumonia, acute respiratory distress syndrome, myocardial injury, thromboembolism, and acute kidney injury. Medication strategies have involved minimizing the spread of the virus through antiviral medications (monoclonal antibodies or nucleotide reverse transcriptase inhibitors). Here, we develop a mathematical model that simulates viral dynamics in an untreated individual, and the evaluate the impact that a monoclonal antibody can have on slowing viral replication. Drug pharmacokinetics (PK) was informed by a typical two-compartment PK model with parameters typical of a monoclonal antibody, with a third compartment for the lung included as the drug site of action. The viral dynamics were captured using a simplified model describing uninfected target cells, infected target cells, and viral load in the body. The mechanism of action of the simulated antiviral is based on binding to the virus, thereby preventing it from infecting healthy cells. The model is used to project dosages needed to prevent severe disease under a variety of simulated conditions and subject to realistic constraints. The proposed model can capture a variety of scenarios of longitudinal viral dynamics and assess the impact of antiviral therapy on disease severity and duration. The described approach can be easily adapted to rapidly assess the dosages needed to affect duration and outcome of other viral infections and can serve as part of a fast and efficient scientific and modeling response strategy in the future as needed , IFAC (International Federation of Automatic Control) Hosting by Elsevier Ltd. 2022 2023-02-07 /pmc/articles/PMC9903140/ http://dx.doi.org/10.1016/j.ifacol.2023.01.038 Text en © 2019, IFAC (International Federation of Automatic Control) Hosting by Elsevier Ltd. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
Kareva, Irina
Zutshi, Anup
Madrasi, Kumpal
Mathematical modeling of SARS-CoV-2 viral dynamics and treatment with monoclonal antibodies
title Mathematical modeling of SARS-CoV-2 viral dynamics and treatment with monoclonal antibodies
title_full Mathematical modeling of SARS-CoV-2 viral dynamics and treatment with monoclonal antibodies
title_fullStr Mathematical modeling of SARS-CoV-2 viral dynamics and treatment with monoclonal antibodies
title_full_unstemmed Mathematical modeling of SARS-CoV-2 viral dynamics and treatment with monoclonal antibodies
title_short Mathematical modeling of SARS-CoV-2 viral dynamics and treatment with monoclonal antibodies
title_sort mathematical modeling of sars-cov-2 viral dynamics and treatment with monoclonal antibodies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9903140/
http://dx.doi.org/10.1016/j.ifacol.2023.01.038
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