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

Perelson, Alan S.; Ke, Ruian

doi:10.1002/cpt.2160

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

Journal Article · 19 January 2020 · Clinical Pharmacology and Therapeutics

DOI: https://doi.org/10.1002/cpt.2160 · OSTI ID:1764237

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Los Alamos National Lab. (LANL), Los Alamos, NM (United States); New Mexico Consortium, Los Alamos, NM (United States)

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.

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Research Organization:: Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)

Sponsoring Organization:: Defense Advanced Research Projects Agency (DARPA); National Institutes of Health (NIH); National Science Foundation (NSF); USDOE

Grant/Contract Number:: 89233218CNA000001

OSTI ID:: 1764237

Report Number(s):: LA-UR--20-29392

Journal Information:: Clinical Pharmacology and Therapeutics, Journal Name: Clinical Pharmacology and Therapeutics Journal Issue: 4 Vol. 109; ISSN 0009-9236

Publisher:: American Society for Clinical Pharmacology & Therapeutics - WileyCopyright Statement

Country of Publication:: United States

Language:: English

References (96)

Airborne Transmission of SARS-CoV-2: Theoretical Considerations and Available Evidence Klompas, Michael; Baker, Meghan A.; Rhee, Chanu JAMA, Vol. 324, Issue 5 https://doi.org/10.1001/jama.2020.12458	journal	August 2020
Pharmacodynamics of PEG-IFN α differentiate HIV/HCV coinfected sustained virological responders from nonresponders Talal, Andrew H.; Ribeiro, Ruy M.; Powers, Kimberly A. Hepatology, Vol. 43, Issue 5 https://doi.org/10.1002/hep.21136	journal	May 2006
Modeling viral kinetics and treatment outcome during alisporivir interferon-free treatment in hepatitis C virus genotype 2 and 3 patients: HEPATOLOGY, Vol. XX, NO. X, 2014 GUEDJ ET AL. Guedj, Jeremie; Yu, Jing; Levi, Micha Hepatology, Vol. 59, Issue 5 https://doi.org/10.1002/hep.26989	journal	April 2014
Influenza A virus infection kinetics: quantitative data and models: Modeling influenza kinetics Smith, Amber M.; Perelson, Alan S. Wiley Interdisciplinary Reviews: Systems Biology and Medicine, Vol. 3, Issue 4 https://doi.org/10.1002/wsbm.129	journal	December 2010
Modeling Plasma Virus Concentration during Primary HIV Infection Stafford, Max A.; Corey, Lawrence; Cao, Yunzhen Journal of Theoretical Biology, Vol. 203, Issue 3 https://doi.org/10.1006/jtbi.2000.1076	journal	April 2000
Pharmacodynamics of Antiretroviral Agents in HIV-1 Infected Patients: Using Viral Dynamic Models that Incorporate Drug Susceptibility and Adherence Wu, Hulin; Huang, Yangxin; Acosta, Edward P. Journal of Pharmacokinetics and Pharmacodynamics, Vol. 33, Issue 4 https://doi.org/10.1007/s10928-006-9006-4	journal	April 2006
Pharmacokinetic Basis of the Hydroxychloroquine Response in COVID-19: Implications for Therapy and Prevention Tarek, Mohammad; Savarino, Andrea European Journal of Drug Metabolism and Pharmacokinetics, Vol. 45, Issue 6 https://doi.org/10.1007/s13318-020-00640-6	journal	August 2020
Dynamics of HIV infection of CD4+ T cells Perelson, Alan S.; Kirschner, Denise E.; De Boer, Rob Mathematical Biosciences, Vol. 114, Issue 1 https://doi.org/10.1016/0025-5564(93)90043-A	journal	March 1993
Influence of delayed viral production on viral dynamics in HIV-1 infected patients Mittler, John E.; Sulzer, Bernhard; Neumann, Avidan U. Mathematical Biosciences, Vol. 152, Issue 2 https://doi.org/10.1016/S0025-5564(98)10027-5	journal	September 1998
Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial Wang, Yeming; Zhang, Dingyu; Du, Guanhua The Lancet, Vol. 395, Issue 10236 https://doi.org/10.1016/S0140-6736(20)31022-9	journal	May 2020
Rapid production and clearance of HIV-1 and hepatitis C virus assessed by large volume plasma apheresis Ramratnam, Bharat; Bonhoeffer, Sebastian; Binley, James The Lancet, Vol. 354, Issue 9192 https://doi.org/10.1016/S0140-6736(99)02035-8	journal	November 1999
Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study To, Kelvin Kai-Wang; Tsang, Owen Tak-Yin; Leung, Wai-Shing The Lancet Infectious Diseases, Vol. 20, Issue 5 https://doi.org/10.1016/S1473-3099(20)30196-1	journal	May 2020
SARS-CoV-2 viral load predicts COVID-19 mortality Pujadas, Elisabet; Chaudhry, Fayzan; McBride, Russell The Lancet Respiratory Medicine, Vol. 8, Issue 9 https://doi.org/10.1016/S2213-2600(20)30354-4	journal	September 2020
In-host Mathematical Modelling of COVID-19 in Humans Hernandez-Vargas, Esteban A.; Velasco-Hernandez, Jorge X. Annual Reviews in Control, Vol. 50 https://doi.org/10.1016/j.arcontrol.2020.09.006	journal	January 2020
Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19 Blanco-Melo, Daniel; Nilsson-Payant, Benjamin E.; Liu, Wen-Chun Cell, Vol. 181, Issue 5 https://doi.org/10.1016/j.cell.2020.04.026	journal	May 2020
SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract Hou, Yixuan J.; Okuda, Kenichi; Edwards, Caitlin E. Cell, Vol. 182, Issue 2 https://doi.org/10.1016/j.cell.2020.05.042	journal	July 2020
Antigen-Specific Adaptive Immunity to SARS-CoV-2 in Acute COVID-19 and Associations with Age and Disease Severity Rydyznski Moderbacher, Carolyn; Ramirez, Sydney I.; Dan, Jennifer M. Cell, Vol. 183, Issue 4 https://doi.org/10.1016/j.cell.2020.09.038	journal	November 2020
Targeting the Latent Reservoir for HIV-1 Sengupta, Srona; Siliciano, Robert F. Immunity, Vol. 48, Issue 5 https://doi.org/10.1016/j.immuni.2018.04.030	journal	May 2018
Modeling hepatitis C virus dynamics: Liver regeneration and critical drug efficacy Dahari, Harel; Lo, Arthur; Ribeiro, Ruy M. Journal of Theoretical Biology, Vol. 247, Issue 2 https://doi.org/10.1016/j.jtbi.2007.03.006	journal	July 2007
A PDE multiscale model of hepatitis C virus infection can be transformed to a system of ODEs Kitagawa, Kosaku; Nakaoka, Shinji; Asai, Yusuke Journal of Theoretical Biology, Vol. 448 https://doi.org/10.1016/j.jtbi.2018.04.006	journal	July 2018
Modeling the viral dynamics of SARS-CoV-2 infection Wang, Sunpeng; Pan, Yang; Wang, Quanyi Mathematical Biosciences, Vol. 328 https://doi.org/10.1016/j.mbs.2020.108438	journal	October 2020
Quantifying the effect of remdesivir in rhesus macaques infected with SARS-CoV-2 Dobrovolny, Hana M. Virology, Vol. 550 https://doi.org/10.1016/j.virol.2020.07.015	journal	November 2020
Viral dynamics in human immunodeficiency virus type 1 infection Wei, Xiping; Ghosh, Sajal K.; Taylor, Maria E. Nature, Vol. 373, Issue 6510 https://doi.org/10.1038/373117a0	journal	January 1995
Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection Ho, David D.; Neumann, Avidan U.; Perelson, Alan S. Nature, Vol. 373, Issue 6510 https://doi.org/10.1038/373123a0	journal	January 1995
Decay characteristics of HIV-1-infected compartments during combination therapy Perelson, Alan S.; Essunger, Paulina; Cao, Yunzhen Nature, Vol. 387, Issue 6629 https://doi.org/10.1038/387188a0	journal	May 1997
Latent infection of CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy Finzi, Diana; Blankson, Joel; Siliciano, Janet D. Nature Medicine, Vol. 5, Issue 5 https://doi.org/10.1038/8394	journal	May 1999
A Comprehensive Hepatitis C Viral Kinetic Model Explaining Cure Snoeck, E.; Chanu, P.; Lavielle, M. Clinical Pharmacology & Therapeutics, Vol. 87, Issue 6 https://doi.org/10.1038/clpt.2010.35	journal	May 2010
Emergent properties of the interferon-signalling network may underlie the success of hepatitis C treatment Padmanabhan, Pranesh; Garaigorta, Urtzi; Dixit, Narendra M. Nature Communications, Vol. 5, Issue 1 https://doi.org/10.1038/ncomms4872	journal	May 2014
Modelling viral and immune system dynamics Perelson, Alan S. Nature Reviews Immunology, Vol. 2, Issue 1 https://doi.org/10.1038/nri700	journal	January 2002
SARS-CoV-2 viral load is associated with increased disease severity and mortality Fajnzylber, Jesse; Regan, James; Coxen, Kendyll Nature Communications, Vol. 11, Issue 1 https://doi.org/10.1038/s41467-020-19057-5	journal	October 2020
The trinity of COVID-19: immunity, inflammation and intervention Tay, Matthew Zirui; Poh, Chek Meng; Rénia, Laurent Nature Reviews Immunology, Vol. 20, Issue 6 https://doi.org/10.1038/s41577-020-0311-8	journal	April 2020
Virological assessment of hospitalized patients with COVID-2019 Wölfel, Roman; Corman, Victor M.; Guggemos, Wolfgang Nature, Vol. 581, Issue 7809 https://doi.org/10.1038/s41586-020-2196-x	journal	April 2020
Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2 Williamson, Brandi N.; Feldmann, Friederike; Schwarz, Benjamin Nature, Vol. 585, Issue 7824 https://doi.org/10.1038/s41586-020-2423-5	journal	June 2020
Longitudinal analyses reveal immunological misfiring in severe COVID-19 Lucas, Carolina; Wong, Patrick; Klein, Jon Nature, Vol. 584, Issue 7821 https://doi.org/10.1038/s41586-020-2588-y	journal	July 2020
SARS-CoV-2-reactive T cells in healthy donors and patients with COVID-19 Braun, Julian; Loyal, Lucie; Frentsch, Marco Nature, Vol. 587, Issue 7833 https://doi.org/10.1038/s41586-020-2598-9	journal	July 2020
SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes Sungnak, Waradon; Huang, Ni; Bécavin, Christophe Nature Medicine, Vol. 26, Issue 5 https://doi.org/10.1038/s41591-020-0868-6	journal	April 2020
Temporal dynamics in viral shedding and transmissibility of COVID-19 He, Xi; Lau, Eric H. Y.; Wu, Peng Nature Medicine, Vol. 26, Issue 5 https://doi.org/10.1038/s41591-020-0869-5	journal	April 2020
Duration of SHIV production by infected cells is not exponentially distributed: Implications for estimates of infection parameters and antiviral efficacy Beauchemin, Catherine A. A.; Miura, Tomoyuki; Iwami, Shingo Scientific Reports, Vol. 7, Issue 1 https://doi.org/10.1038/srep42765	journal	February 2017
Short-term antiviral efficacy of BILN 2061, a hepatitis C virus serine protease inhibitor, in hepatitis C genotype 1 patients Hinrichsen, Holger; Benhamou, Yves; Wedemeyer, Heiner Gastroenterology, Vol. 127, Issue 5 https://doi.org/10.1053/j.gastro.2004.08.002	journal	November 2004
Kinetic Analyses Reveal Potent and Early Blockade of Hepatitis C Virus Assembly by NS5A Inhibitors McGivern, David R.; Masaki, Takahiro; Williford, Sara Gastroenterology, Vol. 147, Issue 2 https://doi.org/10.1053/j.gastro.2014.04.021	journal	August 2014
Natural History of Asymptomatic SARS-CoV-2 Infection Sakurai, Aki; Sasaki, Toshiharu; Kato, Shigeo New England Journal of Medicine, Vol. 383, Issue 9 https://doi.org/10.1056/NEJMc2013020	journal	August 2020
Remdesivir for the Treatment of Covid-19 — Final Report Beigel, John H.; Tomashek, Kay M.; Dodd, Lori E. New England Journal of Medicine, Vol. 383, Issue 19 https://doi.org/10.1056/NEJMoa2007764	journal	November 2020
Variation in HIV-1 set-point viral load: Epidemiological analysis and an evolutionary hypothesis Fraser, C.; Hollingsworth, T. D.; Chapman, R. Proceedings of the National Academy of Sciences, Vol. 104, Issue 44 https://doi.org/10.1073/pnas.0708559104	journal	October 2007
Modeling shows that the NS5A inhibitor daclatasvir has two modes of action and yields a shorter estimate of the hepatitis C virus half-life Guedj, J.; Dahari, H.; Rong, L. Proceedings of the National Academy of Sciences, Vol. 110, Issue 10 https://doi.org/10.1073/pnas.1203110110	journal	February 2013
Zika plasma viral dynamics in nonhuman primates provides insights into early infection and antiviral strategies Best, Katharine; Guedj, Jeremie; Madelain, Vincent Proceedings of the National Academy of Sciences, Vol. 114, Issue 33 https://doi.org/10.1073/pnas.1704011114	journal	August 2017
A dynamical motif comprising the interactions between antigens and CD8 T cells may underlie the outcomes of viral infections Baral, Subhasish; Antia, Rustom; Dixit, Narendra M. Proceedings of the National Academy of Sciences, Vol. 116, Issue 35 https://doi.org/10.1073/pnas.1902178116	journal	August 2019
Characterizing superspreading events and age-specific infectiousness of SARS-CoV-2 transmission in Georgia, USA Lau, Max S. Y.; Grenfell, Bryan; Thomas, Michael Proceedings of the National Academy of Sciences, Vol. 117, Issue 36 https://doi.org/10.1073/pnas.2011802117	journal	August 2020
In silico dynamics of COVID-19 phenotypes for optimizing clinical management Voutouri, Chrysovalantis; Nikmaneshi, Mohammad Reza; Hardin, C. Corey Proceedings of the National Academy of Sciences, Vol. 118, Issue 3 https://doi.org/10.1073/pnas.2021642118	journal	January 2021
Viral dynamics in vivo: limitations on estimates of intracellular delay and virus decay. Herz, A. V.; Bonhoeffer, S.; Anderson, R. M. Proceedings of the National Academy of Sciences, Vol. 93, Issue 14 https://doi.org/10.1073/pnas.93.14.7247	journal	July 1996
Antibody potency, effector function, and combinations in protection and therapy for SARS-CoV-2 infection in vivo Schäfer, Alexandra; Muecksch, Frauke; Lorenzi, Julio C. C. Journal of Experimental Medicine, Vol. 218, Issue 3 https://doi.org/10.1084/jem.20201993	journal	November 2020
Determining the Relative Efficacy of Highly Active Antiretroviral Therapy Louie, Michael; Hogan, Christine; Di Mascio, Michele The Journal of Infectious Diseases, Vol. 187, Issue 6 https://doi.org/10.1086/368164	journal	March 2003
Combination Antiviral Therapy for Influenza: Predictions From Modeling of Human Infections Perelson, Alan S.; Rong, Libin; Hayden, Frederick G. The Journal of Infectious Diseases, Vol. 205, Issue 11 https://doi.org/10.1093/infdis/jis265	journal	March 2012
Modelling clinical data shows active tissue concentration of daclatasvir is 10-fold lower than its plasma concentration Ke, R.; Loverdo, C.; Qi, H. Journal of Antimicrobial Chemotherapy, Vol. 69, Issue 3 https://doi.org/10.1093/jac/dkt423	journal	October 2013
Improved estimates for H1V-1 clearance rate and intracellular delay Mittler, John E.; Markowitz, Martin; Ho, David D. AIDS, Vol. 13, Issue 11 https://doi.org/10.1097/00002030-199907300-00023	journal	January 1999
Modeling Long-Term HIV Dynamics and Antiretroviral Response: Effects of Drug Potency, Pharmacokinetics, Adherence, and Drug Resistance Wu, Hulin; Huang, Yangxin; Acosta, Edward P. JAIDS Journal of Acquired Immune Deficiency Syndromes, Vol. 39, Issue 3 https://doi.org/10.1097/01.qai.0000165907.04710.da	journal	January 2005
Density-Dependent Decay in HIV-1 Dynamics Holte, Sarah E.; Melvin, Ann J.; Mullins, James I. JAIDS Journal of Acquired Immune Deficiency Syndromes, Vol. 41, Issue 3 https://doi.org/10.1097/01.qai.0000199233.69457.e4	journal	January 2006
Estimating biologically relevant parameters under uncertainty for experimental within-host murine West Nile virus infection Banerjee, Soumya; Guedj, Jeremie; Ribeiro, Ruy M. Journal of The Royal Society Interface, Vol. 13, Issue 117 https://doi.org/10.1098/rsif.2016.0130	journal	April 2016
Mathematical modelling identifies the role of adaptive immunity as a key controller of respiratory syncytial virus in cotton rats Wethington, Darren; Harder, Olivia; Uppulury, Karthik Journal of The Royal Society Interface, Vol. 16, Issue 160 https://doi.org/10.1098/rsif.2019.0389	journal	November 2019
Crossing the scale from within-host infection dynamics to between-host transmission fitness: a discussion of current assumptions and knowledge Handel, Andreas; Rohani, Pejman Philosophical Transactions of the Royal Society B: Biological Sciences, Vol. 370, Issue 1675 https://doi.org/10.1098/rstb.2014.0302	journal	August 2015
SARS-coronavirus-2 replication in Vero E6 cells: replication kinetics, rapid adaptation and cytopathology Ogando, Natacha S.; Dalebout, Tim J.; Zevenhoven-Dobbe, Jessika C. Journal of General Virology, Vol. 101, Issue 9 https://doi.org/10.1099/jgv.0.001453	journal	September 2020
Mathematical modeling of within-host Zika virus dynamics Best, Katharine; Perelson, Alan S. Immunological Reviews, Vol. 285, Issue 1 https://doi.org/10.1111/imr.12687	journal	August 2018
Potency and timing of antiviral therapy as determinants of duration of SARS-CoV-2 shedding and intensity of inflammatory response Goyal, Ashish; Cardozo-Ojeda, E. Fabian; Schiffer, Joshua T. Science Advances, Vol. 6, Issue 47 https://doi.org/10.1126/sciadv.abc7112	journal	October 2020
HIV-1 Dynamics in Vivo: Virion Clearance Rate, Infected Cell Life-Span, and Viral Generation Time Perelson, A. S.; Neumann, A. U.; Markowitz, M. Science, Vol. 271, Issue 5255 https://doi.org/10.1126/science.271.5255.1582	journal	March 1996
Hepatitis C Viral Dynamics in Vivo and the Antiviral Efficacy of Interferon- Therapy Neumann, A. U. Science, Vol. 282, Issue 5386 https://doi.org/10.1126/science.282.5386.103	journal	October 1998
Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients Hadjadj, Jérôme; Yatim, Nader; Barnabei, Laura Science, Vol. 369, Issue 6504 https://doi.org/10.1126/science.abc6027	journal	July 2020
Serial interval of SARS-CoV-2 was shortened over time by nonpharmaceutical interventions Ali, Sheikh Taslim; Wang, Lin; Lau, Eric H. Y. Science, Vol. 369, Issue 6507 https://doi.org/10.1126/science.abc9004	journal	July 2020
Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody cocktail Hansen, Johanna; Baum, Alina; Pascal, Kristen E. Science https://doi.org/10.1126/science.abd0827	journal	June 2020
Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies Baum, Alina; Fulton, Benjamin O.; Wloga, Elzbieta Science https://doi.org/10.1126/science.abd0831	journal	June 2020
Inborn errors of type I IFN immunity in patients with life-threatening COVID-19 Zhang, Qian; Bastard, Paul; Liu, Zhiyong Science, Vol. 370, Issue 6515 https://doi.org/10.1126/science.abd4570	journal	September 2020
Autoantibodies against type I IFNs in patients with life-threatening COVID-19 Bastard, Paul; Rosen, Lindsey B.; Zhang, Qian Science, Vol. 370, Issue 6515 https://doi.org/10.1126/science.abd4585	journal	September 2020
REGN-COV2 antibodies prevent and treat SARS-CoV-2 infection in rhesus macaques and hamsters Baum, Alina; Ajithdoss, Dharani; Copin, Richard Science, Vol. 370, Issue 6520 https://doi.org/10.1126/science.abe2402	journal	October 2020
Phenotype and kinetics of SARS-CoV-2-specific T cells in COVID-19 patients with acute respiratory distress syndrome Weiskopf, Daniela; Schmitz, Katharina S.; Raadsen, Matthijs P. Science Immunology, Vol. 5, Issue 48 https://doi.org/10.1126/sciimmunol.abd2071	journal	June 2020
Rapid Emergence of Protease Inhibitor Resistance in Hepatitis C Virus Rong, L.; Dahari, H.; Ribeiro, R. M. Science Translational Medicine, Vol. 2, Issue 30 https://doi.org/10.1126/scitranslmed.3000544	journal	May 2010
Kinetics of Influenza A Virus Infection in Humans Baccam, P.; Beauchemin, C.; Macken, C. A. Journal of Virology, Vol. 80, Issue 15 https://doi.org/10.1128/JVI.01623-05	journal	July 2006
Protease Inhibitors Block Multiple Functions of the NS3/4A Protease-Helicase during the Hepatitis C Virus Life Cycle McGivern, David R.; Masaki, Takahiro; Lovell, William Journal of Virology, Vol. 89, Issue 10 https://doi.org/10.1128/JVI.03188-14	journal	March 2015
A Novel Antiviral Intervention Results in More Accurate Assessment of Human Immunodeficiency Virus Type 1 Replication Dynamics and T-Cell Decay In Vivo Markowitz, M.; Louie, M.; Hurley, A. Journal of Virology, Vol. 77, Issue 8 https://doi.org/10.1128/JVI.77.8.5037-5038.2003	journal	April 2003
Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: retrospective cohort study Zheng, Shufa; Fan, Jian; Yu, Fei BMJ https://doi.org/10.1136/bmj.m1443	journal	April 2020
Mathematical Analysis of HIV-1 Dynamics in Vivo Perelson, Alan S.; Nelson, Patrick W. SIAM Review, Vol. 41, Issue 1 https://doi.org/10.1137/S0036144598335107	journal	January 1999
IFN-I response timing relative to virus replication determines MERS coronavirus infection outcomes Channappanavar, Rudragouda; Fehr, Anthony R.; Zheng, Jian Journal of Clinical Investigation, Vol. 129, Issue 9 https://doi.org/10.1172/JCI126363	journal	July 2019
Type 2 alveolar cells are stem cells in adult lung Barkauskas, Christina E.; Cronce, Michael J.; Rackley, Craig R. Journal of Clinical Investigation, Vol. 123, Issue 7 https://doi.org/10.1172/JCI68782	journal	June 2013
Exploring the effect of biological delays in kinetic models of influenza within a host or cell culture Holder, Benjamin P.; Beauchemin, Catherine AA BMC Public Health, Vol. 11, Issue Suppl 1 https://doi.org/10.1186/1471-2458-11-S1-S10	journal	January 2011
Modeling the within-host dynamics of HIV infection Perelson, Alan S.; Ribeiro, Ruy M. BMC Biology, Vol. 11, Issue 1 https://doi.org/10.1186/1741-7007-11-96	journal	September 2013
Neuraminidase Inhibitor Resistance in Influenza: Assessing the Danger of Its Generation and Spread Handel, Andreas; Longini, Ira M.; Antia, Rustom PLoS Computational Biology, Vol. 3, Issue 12 https://doi.org/10.1371/journal.pcbi.0030240	journal	December 2007
Stochastic Theory of Early Viral Infection: Continuous versus Burst Production of Virions Pearson, John E.; Krapivsky, Paul; Perelson, Alan S. PLoS Computational Biology, Vol. 7, Issue 2 https://doi.org/10.1371/journal.pcbi.1001058	journal	February 2011
Modeling Within-Host Dynamics of Influenza Virus Infection Including Immune Responses Pawelek, Kasia A.; Huynh, Giao T.; Quinlivan, Michelle PLoS Computational Biology, Vol. 8, Issue 6 https://doi.org/10.1371/journal.pcbi.1002588	journal	June 2012
A modular framework for multiscale, multicellular, spatiotemporal modeling of acute primary viral infection and immune response in epithelial tissues and its application to drug therapy timing and effectiveness Sego, T. J.; Aponte-Serrano, Josua O.; Ferrari Gianlupi, Juliano PLOS Computational Biology, Vol. 16, Issue 12 https://doi.org/10.1371/journal.pcbi.1008451	journal	December 2020
Zika virus dynamics: Effects of inoculum dose, the innate immune response and viral interference Best, Katharine; Barouch, Dan H.; Guedj, Jeremie PLOS Computational Biology, Vol. 17, Issue 1 https://doi.org/10.1371/journal.pcbi.1008564	journal	January 2021
Modeling the Viral Dynamics of Influenza A Virus Infection Smith, Amber M.; Ribeiro, Ruy M. Critical Reviews™ in Immunology, Vol. 30, Issue 3 https://doi.org/10.1615/CritRevImmunol.v30.i3.60	journal	January 2010
Principles of Effective and Robust Innate Immune Response to Viral Infections: A Multiplex Network Analysis Huang, Yufan; Dai, Huaiyu; Ke, Ruian Frontiers in Immunology, Vol. 10 https://doi.org/10.3389/fimmu.2019.01736	journal	July 2019
Influenza Virus Infection Model With Density Dependence Supports Biphasic Viral Decay Smith, Amanda P.; Moquin, David J.; Bernhauerova, Veronika Frontiers in Microbiology, Vol. 9 https://doi.org/10.3389/fmicb.2018.01554	journal	July 2018
Causes and Consequences of Spatial Within-Host Viral Spread Gallagher, Molly; Brooke, Christopher; Ke, Ruian Viruses, Vol. 10, Issue 11 https://doi.org/10.3390/v10110627	journal	November 2018
Simple Mathematical Models Do Not Accurately Predict Early SIV Dynamics Noecker, Cecilia; Schaefer, Krista; Zaccheo, Kelly Viruses, Vol. 7, Issue 3 https://doi.org/10.3390/v7031189	journal	March 2015
The Role of Infected Cell Proliferation in the Clearance of Acute HBV Infection in Humans Goyal, Ashish; Ribeiro, Ruy; Perelson, Alan Viruses, Vol. 9, Issue 11 https://doi.org/10.3390/v9110350	journal	November 2017
A pharmacokinetic/viral kinetic model to evaluate the treatment effectiveness of danoprevir against chronic HCV Canini, Laetitia; Chatterjee, Anushree; Guedj, Jeremie Antiviral Therapy, Vol. 20, Issue 5 https://doi.org/10.3851/IMP2879	journal	January 2014
An Age-Structured Model of HIV Infection that Allows for Variations in the Production Rate of Viral Particles and the Death Rate of Productively Infected Cells Nelson, Patrick W.; Gilchrist, Michael A.; Coombs, Daniel Mathematical Biosciences and Engineering, Vol. 1, Issue 2 https://doi.org/10.3934/mbe.2004.1.267	journal	July 2004
Different Dynamics of CD4 ⁺ and CD8 ⁺ T Cell Responses During and After Acute Lymphocytic Choriomeningitis Virus Infection De Boer, Rob J.; Homann, Dirk; Perelson, Alan S. The Journal of Immunology, Vol. 171, Issue 8 https://doi.org/10.4049/jimmunol.171.8.3928	journal	October 2003

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60 APPLIED LIFE SCIENCES
COVID-19
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hepatitis C
influenza

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

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