June 8, 2020

InSysBio has performed the first step in the direction of development of QSP model of COVID-19 describing virus and host cell life cycles, innate and adoptive immune response and possible therapeutic treatments.

Model description:

InSysBio team has developed the first version of sub-model which describes virus and host cell life cycles. Scheme of the sub-model was presented a week ago. The model represents infection of alveolar cell type II (ATII pneumocytes type II) with SARS-CoV-2 via binding to ACE2 located on the cell surface. Virus-ACE2 complex is internalized with subsequent virus penetration to cytoplasm, uncoating, replication, assembling of newly produced viral particles and their release. Model is preliminary calibrated against available data displaying lung physiology, SARS-CoV-2 structure, in vitro data describing ACE2 binding to Spike protein, in vivo data describing ATII life cycle in healthy subjects etc.

Immune Response was introduced in empiric way as was covered in materials available at https://github.com/insysbio/covid19-qsp-model

Results:

(1) Model allows to reproduce average data on:

• viral load taken from different;
• % of viral subgenomic mRNA in sputum.

(2) Model simulations pushes us to conclude that:

• there is a threshold in virus initial concentration;
• The values above the threshold lead to substantial and transient virus load in sputum;
• The values below the threshold do not allow detect virus in sputum at any time;
• Increase in virus initial concentration results in higher peak of viral load which is faster achieved.

Limitations of the version of the sub-model:

• IR was described in empiric way;
• antiviral IFN type I effect was not implemented;
• sub-model describes scenario when 100% of lungs are infected with virus but most patients demonstrate partial lung injury only;
• uncertainty in parameter values has not been explored.

About InSysBio

InSysBio is a Quantitative Systems Pharmacology (QSP) company located in Moscow, Russia (INSYSBIO LLC) and Edinburgh, UK (INSYSBIO UK LIMITED). InSysBio was founded in 2004 and has an extensive track record of helping pharmaceutical companies to make right decisions on the critical stages of drug research and development by application of QSP modeling. InSysBio’s innovative QSP approach has already become a part of the drug development process implemented by our strategic partners: there are more than 100 completed projects in collaboration with leaders of pharmaceutical industry. For more information about InSysBio, its solutions and services, visit www.insysbio.com.

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