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Title: Mechanistic modelling of SARS-CoV-2 and other infectious diseases and the effects of therapeutics

Abstract

Modern viral kinetic modeling and its application to therapeutics is a field that attracted the attention of the medical, pharmaceutical and modeling communities during the early days of the AIDS epidemic. Its successes lead to applications of modeling methods not only to HIV but a plethora of other viruses, such as hepatitis C virus (HCV), hepatitis B virus (HBV) and cytomegalovirus (CMV), which along with HIV cause chronic diseases, and viruses such as influenza, respiratory syncytial virus (RSV), West Nile virus (WNV), Zika virus, and SAR-CoV-2, which generally cause acute infections. Here we first review the historical development of mathematical models to understand HIV and HCV infections and the effects of treatment by fitting the models to clinical data. Furthermore, we then focus on recent efforts and contributions of applying these models towards understanding SARS-CoV-2 infection and highlight outstanding questions where modeling can provide crucial insights and help to optimize non-pharmaceutical and pharmaceutical interventions of the COVID-19 pandemic. The review is written from our personal perspective emphasizing the power of simple target cell limited models that provided important insights and then their evolution into more complex models that captured more of the virology and immunology. To quote Albert Einstein “Everythingmore » should be made as simple as possible, but not simpler”, and this idea underlies the modeling we describe below.« less

Authors:
ORCiD logo [1]; ORCiD logo [1]
  1. Los Alamos National Lab. (LANL), Los Alamos, NM (United States); New Mexico Consortium, Los Alamos, NM (United States)
Publication Date:
Research Org.:
Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Sponsoring Org.:
USDOE; National Institutes of Health (NIH); Defense Advanced Research Projects Agency (DARPA); National Science Foundation (NSF)
OSTI Identifier:
1764237
Report Number(s):
LA-UR-20-29392
Journal ID: ISSN 0009-9236
Grant/Contract Number:  
89233218CNA000001; R01-OD011095; R01-AI028433; R01-AI15270301; PHY-2031756
Resource Type:
Accepted Manuscript
Journal Name:
Clinical Pharmacology and Therapeutics
Additional Journal Information:
Journal Volume: 109; Journal Issue: 4; Journal ID: ISSN 0009-9236
Publisher:
American Society for Clinical Pharmacology & Therapeutics - Wiley
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; Viral dynamics; SARS-CoV-2; COVID-19; HIV; hepatitis C; influenza

Citation Formats

Perelson, Alan S., and Ke, Ruian. Mechanistic modelling of SARS-CoV-2 and other infectious diseases and the effects of therapeutics. United States: N. p., 2020. Web. doi:10.1002/cpt.2160.
Perelson, Alan S., & Ke, Ruian. Mechanistic modelling of SARS-CoV-2 and other infectious diseases and the effects of therapeutics. United States. https://doi.org/10.1002/cpt.2160
Perelson, Alan S., and Ke, Ruian. Sun . "Mechanistic modelling of SARS-CoV-2 and other infectious diseases and the effects of therapeutics". United States. https://doi.org/10.1002/cpt.2160. https://www.osti.gov/servlets/purl/1764237.
@article{osti_1764237,
title = {Mechanistic modelling of SARS-CoV-2 and other infectious diseases and the effects of therapeutics},
author = {Perelson, Alan S. and Ke, Ruian},
abstractNote = {Modern viral kinetic modeling and its application to therapeutics is a field that attracted the attention of the medical, pharmaceutical and modeling communities during the early days of the AIDS epidemic. Its successes lead to applications of modeling methods not only to HIV but a plethora of other viruses, such as hepatitis C virus (HCV), hepatitis B virus (HBV) and cytomegalovirus (CMV), which along with HIV cause chronic diseases, and viruses such as influenza, respiratory syncytial virus (RSV), West Nile virus (WNV), Zika virus, and SAR-CoV-2, which generally cause acute infections. Here we first review the historical development of mathematical models to understand HIV and HCV infections and the effects of treatment by fitting the models to clinical data. Furthermore, we then focus on recent efforts and contributions of applying these models towards understanding SARS-CoV-2 infection and highlight outstanding questions where modeling can provide crucial insights and help to optimize non-pharmaceutical and pharmaceutical interventions of the COVID-19 pandemic. The review is written from our personal perspective emphasizing the power of simple target cell limited models that provided important insights and then their evolution into more complex models that captured more of the virology and immunology. To quote Albert Einstein “Everything should be made as simple as possible, but not simpler”, and this idea underlies the modeling we describe below.},
doi = {10.1002/cpt.2160},
journal = {Clinical Pharmacology and Therapeutics},
number = 4,
volume = 109,
place = {United States},
year = {Sun Jan 19 00:00:00 EST 2020},
month = {Sun Jan 19 00:00:00 EST 2020}
}

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