SARS-CoV-2 signaling and interactions with stimulant drugs of abuse via Sigma-1R: Impact on the BBB

NIH Pandemic-Era Grants

Pandemic Era Grants

2022

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Principal Investigator: Gabriela Cristina Brailoiu
Organization: TEMPLE UNIV OF THE COMMONWEALTH
Fiscal Year: 2022
Award: $493,148
Funding agency: National Institute on Drug Abuse

SARS-CoV-2, the virus that causes COVID-10, impacts
multiple organ systems including the central nervous system. Neurological symptoms are seen in about
one third of COVID-19 patients and the virus has been found in brain tissue. SARS-CoV-2 uses
angiotensin converting enzyme 2 (ACE2) located on cell surfaces for entry into cells, and the spike
protein of the virus is the key recognition element for ACE2. ACE2 is expressed by endothelial cells of
the cerebral vasculature that comprise the blood-brain barrier (BBB), the main barrier to entry of
pathogens and toxins into the CNS. Recently, SARS-CoV-2 spike protein has been shown to alter BBB
function using in vitro model systems. Many drugs of abuse, including psychostimulants, negatively
impact BBB function as well. Therefore, it is likely that SARS-CoV-e infection in the presence of
psychostimulants could result in greater damage ot the BBB, further increasing barrier permeability and
resulting in CNS injury. Thus, investigation of the mechanisms underlying the interactions of SARSCoV-
2 and stimulants on the BBB is needed.

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