July 24, 2020

InSysBio has presented a new portion of results in the framework of development of COVID-19 QSP model.

Model description:

InSysBio team has upgraded sub-model (version VL_v0.1.3) describing virus and host cell life cycles. Scheme of the sub-model was presented more than a month ago. The model covers 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, replicating, assembling newly produced viral particles and their release. Model is preliminary calibrated against available data describing 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 described in materials available at https://github.com/insysbio/covid19-qsp-model

Results:

(1) Upgraded model allows to reproduce average data on:

• viral load taken from different sources (doi.org/10.1101/2020.03.05.20030502, [PMID 32315724]);
• % of viral subgenomic mRNA in sputum (doi.org/10.1101/2020.03.05.20030502).

(2) Model simulations pushes us to conclude that delay in induction of Immune Response has a substantial effect on viral load dynamics. Indeed,

• Early Immune Response induction does not allow to detect virus in sputum at any time;
• Delay in IR start substantially increases peak viral load and shifts the peak to later time;
• Very late IR start leads to plateau in viral load dynamics with maximal viral load value.

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.

Share