Sensitivity of SARS-CoV-2 Life Cycle to IFN Effects and ACE2 Binding Unveiled with a Stochastic Model.

Igor Sazonov, Dmitry Grebennikov, Andreas Meyerhans, Gennady Bocharov
Author Information
  1. Igor Sazonov: Faculty of Science and Engineering, Swansea University, Bay Campus, Fabian Way, Swansea SA1 8EN, UK. ORCID
  2. Dmitry Grebennikov: Marchuk Institute of Numerical Mathematics, Russian Academy of Sciences (INM RAS), 119333 Moscow, Russia. ORCID
  3. Andreas Meyerhans: Institució Catalana de Recerca i Estudis Avançats (ICREA), Pg. Lluis Companys 23, 08010 Barcelona, Spain. ORCID
  4. Gennady Bocharov: Marchuk Institute of Numerical Mathematics, Russian Academy of Sciences (INM RAS), 119333 Moscow, Russia. ORCID

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.

Keywords

References

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MeSH Term

Angiotensin-Converting Enzyme 2
Computer Simulation
Humans
Interferon Type I
Kinetics
Life Cycle Stages
Markov Chains
Models, Theoretical
Protein Binding
SARS-CoV-2
Stochastic Processes

Chemicals

Interferon Type I
Angiotensin-Converting Enzyme 2

Word Cloud

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