We have established a human iPS-derived neuronal-glial cell model system that we are using to (1) study A?O-induced neuronal cell cycle reentry (CCR) as well as (2) screen for compounds that inhibit A?O-induced neuronal CCR. We now propose to adapt this cell-based model system to evaluate the effects on SARS-CoV-2 spike protein-ACE2 binding on neuronal ?fitness?, responsiveness and intracellular signaling as well as use to screen for small molecule inhibitors that may used for the next generation SARS-CoV-2 therapeutics.
We propose to adapt of iPS neuron-based 96 well screening format such that we can screen for small molecule inhibitors of the SARS-CoV-2-RBD binding event to ACE2. We will also characterize the biological response SARS-CoV-2-RBD:ACE2 binding on neuronal responsiveness. These data will enable future large screening for SARS-CoV-2 therapeutics as well as enable the development of pharmacodynamic endpoint assays.
