An understanding of the transplacental transport of the SARS-CoV-2 virion is of enormous importance. Objective characterization of virion transport, even in animal models, is a hugely challenging task. Using transplacental transport as an example, we seek to address this problem: we will design and build a Virion Surrogate Particle (VSP). Binding of the VSP to target receptors (ACE2), and subsequent internalization will be validated in cell culture, followed by in vivo testing of transplacental transport.
The specific aims for this supplement are thereore: 1. Prepare Virus Surrogate Particles (VSP), recapitulating the viral lipid envelope, bearing the Spike protein S on the surface and carrying proteolytic Furin in the lumen, and validate binding of VSP to the ACE2 receptor in cell culture studies. 2. Study trans-placental transport of VSP in the k18-hACE2 mouse model with the humanized ACE2 receptor throughout the course of pregnancy using MR, CT and fluorescence tracing of particles 3. Study the effect of known ACE2 receptor level effectors (low protein diet, hypertension, high fat diet) on transplacental transport of VSP
An understanding of the transplacental transport of the SARS-CoV-2 virion is of enormous importance. we will design and build a Virion Surrogate Particle (VSP). Binding of the VSP to target receptors (ACE2), and subsequent internalization will be validated in cell culture, followed by in vivo testing of transplacental transport.
