Journal
EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE
Volume 271, Issue 2, Pages 249-258Publisher
SPRINGER HEIDELBERG
DOI: 10.1007/s00406-020-01231-x
Keywords
Endoplasmic reticulum; Replication; Sigma-1 receptor
Categories
Funding
- Japan Society for the Promotion of Science [17H04243, 19H05203]
- Japan Agency for Medical Research and Development, AMED [JP20dm0107119]
- Grants-in-Aid for Scientific Research [17H04243, 19H05203] Funding Source: KAKEN
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The COVID-19 pandemic caused by SARS-CoV-2 has spurred the search for effective treatments. Research has shown the significance of the sigma-1 receptor in SARS-CoV-2 replication, suggesting the repurposing of CNS drugs targeting this receptor for treatment. Promising results from trials with fluvoxamine have highlighted the potential for antidepressants in preventing clinical deterioration in COVID-19 patients.
The novel coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The escalating number of SARS-CoV-2-infected individuals has conferred the viral spread with the status of global pandemic. However, there are no prophylactic or therapeutic drugs available on the market to treat COVID-19, although several drugs have been approved. Recently, two articles using the comparative viral-human protein-protein interaction map revealed that the sigma-1 receptor in the endoplasmic reticulum plays an important role in SARS-CoV-2 replication in cells. Knockout and knockdown of SIGMAR1 (sigma-1 receptor, encoded by SIGMAR1) caused robust reductions in SARS-CoV-2 replication, which indicates that the sigma-1 receptor is a key therapeutic target for SARS-CoV-2 replication. Interestingly, a recent clinical trial demonstrated that treatment with the antidepressant fluvoxamine, which has a high affinity at the sigma-1 receptor, could prevent clinical deterioration in adult outpatients infected with SARS-CoV-2. In this review, we discuss the brief history of the sigma-1 receptor and its role in SARS-CoV-2 replication in cells. Here, we propose repurposing of traditional central nervous system (CNS) drugs that have a high affinity at the sigma-1 receptor (i.e., fluvoxamine, donepezil, ifenprodil) for the treatment of SARS-CoV-2-infected patients. Finally, we discussed the potential of other CNS candidates such as cutamesine and arketamine.
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