June 2, 2020

The new open source project to be developed and updated Online

InSysBio, one of the world’s pioneers of Quantitative Systems Pharmacology (QSP) modeling, announces the launch of its fundamentally new project in response to the ongoing global threat, the open source QSP model of COVID-19. In accordance with its mission, which is to assist pharmaceutical industry to speed up the delivery of the cure to patients, InSysBio team could not stay aside. Thus, the aim of the new project is to develop QSP model of COVID-19 describing virus and host cell life cycles, innate and adoptive immune response and possible therapeutic treatments.

Inherently, the ongoing pandemic caused by the novel severe respiratory syndrome coronavirus 2 (SARS-CoV-2) has challenged the global public health. Coronavirus disease 2019 (COVID-19) is associated with several respiratory symptoms that can progress to acute respiratory distress syndrome (ARDS). More than 500 clinical trials have been conducted or are underway with no definitive confidence in the doses, regimens and outcome tested. QSP modeling approach can potentially contribute to the fight of the global public health system with the COVID-19 via increasing certainty in mechanism based understanding of virus interaction with host cell leading to immune response and associated inflammation.

Initially, InSysBio has wide experience in development of QSP platforms of immune response in different diseases and their applications to address specific questions associated with drug research and development. InSysBio team has developed and implemented diverse QSP software infrastructure for internal use, namely:

• Immune Response Template (IRT);
• Cytocon DB;
• Heta language and Heta compiler.

Moreover, InSysBio has expertise in modeling of viral dynamics and multiple antiviral drugs and clinically measured outcomes.

Oleg Demin, CEO of InSysBio, comments on the project, “Taking into consideration all the background we have initiated an open source project focused on development of template QSP model of COVID-19 and appropriate therapies. The template model will being steadily updated enhancing the level of its calibration and improving prediction power”.

Model outline

Actually, QSP model of COVID-19 is a mathematical model developed on the basis of modular approach. Each module, representing life cycle of a particular cell, is developed separately. Cell lifecycle sub-model is ODE system describing dynamics of states of the cell caused by influx, proliferation, differentiation, activation, death and migration between relevant tissues. Cytokine production/release and regulation of all the processes with cytokines/surface molecules is also included in cell lifecycle sub-model. Cell lifecycle sub-model is partially calibrated against in vitro data. Most of the cell lifecycles will be adopted from IRT. These extracted lifecycles will then additionally calibrated against in vivo baseline data describing cell and cytokine concentrations in lung tissue, lymph node and blood extracted from Cytocon DB.

Shedding the light on the future steps, InSysBio team is going to include in the model the following modules:

Virus lifecycle including virus binding to pneumocyte, endocytosis, uncoating, replication, assembly and release;

Host cell life cycle including proliferation of type II pneumocytes, their differentiation to type I pneumocytes, death of both cell types, surfactant and cytokine production by type II cells;

Infected cell responses, including changes in level of secreted molecules, and death;

Neutrophil and PBM/Mph lifecycles as key element of innate immune response;

mDC, NK, CD4+ and CD8+ lifecycles as key elements of adaptive immune response;

Clinically measured outcomes characterizing the disease severity and treatment results.

The open source QSP model of COVID-19: https://github.com/insysbio/covid19-qsp-model

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