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Sensitivity of SARS-CoV-2 Life Cycle to IFN Effects and ACE2 Binding Unveiled with a Stochastic Model.
Sazonov, Igor; Grebennikov, Dmitry; Meyerhans, Andreas; Bocharov, Gennady.
  • Sazonov I; Faculty of Science and Engineering, Swansea University, Bay Campus, Fabian Way, Swansea SA1 8EN, UK.
  • Grebennikov D; Marchuk Institute of Numerical Mathematics, Russian Academy of Sciences (INM RAS), 119333 Moscow, Russia.
  • Meyerhans A; Moscow Center of Fundamental and Applied Mathematics at INM RAS, 119333 Moscow, Russia.
  • Bocharov G; World-Class Research Center "Digital Biodesign and Personalized Healthcare", Sechenov First Moscow State Medical University, 119991 Moscow, Russia.
Viruses ; 14(2)2022 02 15.
Article in English | MEDLINE | ID: covidwho-1687060
ABSTRACT
Mathematical modelling of infection processes in cells is of fundamental interest. It helps to understand the SARS-CoV-2 dynamics in detail and can be useful to define the vulnerability steps targeted by antiviral treatments. We previously developed a deterministic mathematical model of the SARS-CoV-2 life cycle in a single cell. Despite answering many questions, it certainly cannot accurately account for the stochastic nature of an infection process caused by natural fluctuation in reaction kinetics and the small abundance of participating components in a single cell. In the present work, this deterministic model is transformed into a stochastic one based on a Markov Chain Monte Carlo (MCMC) method. This model is employed to compute statistical characteristics of the SARS-CoV-2 life cycle including the probability for a non-degenerate infection process. Varying parameters of the model enables us to unveil the inhibitory effects of IFN and the effects of the ACE2 binding affinity. The simulation results show that the type I IFN response has a very strong effect on inhibition of the total viral progeny whereas the effect of a 10-fold variation of the binding rate to ACE2 turns out to be negligible for the probability of infection and viral production.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Interferon Type I / Angiotensin-Converting Enzyme 2 / SARS-CoV-2 / Models, Theoretical Type of study: Experimental Studies / Prognostic study Limits: Humans Language: English Year: 2022 Document Type: Article Affiliation country: V14020403

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Interferon Type I / Angiotensin-Converting Enzyme 2 / SARS-CoV-2 / Models, Theoretical Type of study: Experimental Studies / Prognostic study Limits: Humans Language: English Year: 2022 Document Type: Article Affiliation country: V14020403