Rapid community-driven development of a SARS-CoV-2 tissue simulator

Yafei Wang; Randy Heiland; Morgan Craig; Courtney L. Davis; Ashlee N Ford Versypt; Adrianne Jenner; Jonathan Ozik; Nicholson Collier; Chase Cockrell; Andrew Becker; Gary An; James A. Glazier; Aarthi Narayanan; Amber M Smith; Paul Macklin

It is important that model development takes into account the types of measurements and biological observations that will be available for later model constraint, calibration, and validation. As participation by the virology and pharmacology communities broadens, we anticipate that this list will grow. While we will endeavor to constrain and validate sub-modules of the model independently, we anticipate human clinical data to not fully determine parameters of the model. To address this concern we will apply a 'virtual population' approach and sensitivity analysis to explore model variability within clinically relevant bounds 42, 43 . To date, we anticipate the following data: 7 Organoid data for viral replication and targeted inhibition Aarthi Narayanan's virology lab is optimizing SARS-CoV-2 cultures in organoid model systems. The viral replication kinetics will be assessed by infection of different lung epithelial, fibroblast and endothelial cells, in addition to standard cell lines such as Vero cells. (Vero cells are likely to be the workhorse for inhibitor assessment studies). Primary cells and/or cell lines will be infected with SARS-CoV-2 at increasing multiplicities of infection and infectious viral titers in the supernatants assessed by plaque assays at multiple time points post initial infection. This will stretch from approximately 3 hours post infection up to 48 hours post infection depending on the cell type and the initial infectious dose of virus.