Repurposing Aminoadamantane Nitrate Compounds to Inhibit SARS-CoV-2 Viral Activity and to Protect the Brain from Viral-Related Damage

Research Objective

The objective is to screen a series of aminoadamantane nitrate compounds for their ability to protect hiPSC-derived neurons from SARS-CoV-2-related damage and to block SARS-CoV-2 activity.

Impact

If successful, our screen would identify a drug candidate for further development that would protect neurons from SARS-CoV-2-related damage and also inhibit SARS-CoV-2 activity.

Major Proposed Activities

  • Screening of nine (9) aminoadamantane nitrate congeners for ability to inhibit NMDAR-mediated current in hiPSC-derived cerebrocortical neurons.
  • Moderate-throughput screening of nine (9) aminoadamantane nitrate congeners in BSL3 facility for cytopathic effect (CPE) of SARS-CoV-2 live virus in monkey Vero cells.
  • Moderate-throughput screening of ‘hits’ of aminoadamantane nitrate congeners in BSL3 facility for cytopathic effect (CPE) of SARS-CoV-2 live virus in monkey Vero cells with full dose-response curve.
  • Viral plaque assays for SARS-CoV-2 for viral titer and full dose-response curve of drug candidates. Field of view microscope provides dynamic tracking of plaques at individual cell death event level.
  • Assess synaptic integrity of hiPSC-derived neurons in co-cultures of SARS-CoV-2-infected monocytoid cells and astrocytes with full dose-response curve of drug candidates.

Finding a drug that positively affected the course of COVID-19 infections by protecting the nervous system AND limiting viral infectivity or virulence would have tremendous benefit for all Californians as well as everyone in the world.