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Headlines 15 How the research works The SARS-CoV-2 virus enters human cells via two primary receptors called ACE2 and TMPRSS2. The ‘neurons in a dish’ developed in the lab express both the receptors ACE2 and TMPRSS2. The expression of the TMPRSS2 receptor peaks with the maturation of these neurons, which might render the mature neurons more vulnerable to SARS-CoV-2 infection. The Otago researchers infected precursor, immature, and mature human neurons with the SARS-CoV-2 virus and observed that the rate of infection is greatest in the mature neurons (see image) compared to the precursor and immature neurons. Although the rate of infection in the mature neurons was low compared to other vulnerable tissues in the human body, the low infection was enough to kill the neurons. The researchers will continue to infect more human neurons with the SARS-CoV-2 virus followed by the investigation of the changes in the expression of genes and proteins in the mature neurons. The profile of proteins secreted from the infected neurons will then be tested to identify potentially toxic biomolecules that could have negative secondary effects on neighbouring neurons. The results from these experiments will indicate whether the emergence of neurological symptoms in COVID-19 patients is due to direct infection of neurons by SARS-CoV-2 or secondary consequences. The findings will help identify potential druggable targets that can either protect the neurons from the virus or evade secondary effects from dying neurons.