Repurposing Aminoadamantane Nitrate Compounds to Inhibit SARS-CoV-2 Viral Activity and to Protect the Brain from Viral-Related Damage
Grant Award Details
Grant Type:
Grant Number:
DISC2COVID19-11811
Investigator(s):
Disease Focus:
Human Stem Cell Use:
Award Value:
$150,000
Status:
Closed
Progress Reports
Reporting Period:
Year 1
Grant Application Details
Application Title:
Repurposing Aminoadamantane Nitrate Compounds to Inhibit SARS-CoV-2 Viral Activity and to Protect the Brain from Viral-Related Damage
Public Abstract:
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
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.
Statement of Benefit to California:
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.
