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

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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.