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Repurposing of CNS drugs to treat COVID-19 infection: targeting the sigma-1 receptor
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...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer Berlin Heidelberg
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785036/ https://www.ncbi.nlm.nih.gov/pubmed/33403480 http://dx.doi.org/10.1007/s00406-020-01231-x |
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author | Hashimoto, Kenji |
author_facet | Hashimoto, Kenji |
author_sort | Hashimoto, Kenji |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7785036 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-77850362021-01-06 Repurposing of CNS drugs to treat COVID-19 infection: targeting the sigma-1 receptor Hashimoto, Kenji Eur Arch Psychiatry Clin Neurosci Invited Review 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. Springer Berlin Heidelberg 2021-01-05 2021 /pmc/articles/PMC7785036/ /pubmed/33403480 http://dx.doi.org/10.1007/s00406-020-01231-x Text en © Springer-Verlag GmbH, DE part of Springer Nature 2021 This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic. |
spellingShingle | Invited Review Hashimoto, Kenji Repurposing of CNS drugs to treat COVID-19 infection: targeting the sigma-1 receptor |
title | Repurposing of CNS drugs to treat COVID-19 infection: targeting the sigma-1 receptor |
title_full | Repurposing of CNS drugs to treat COVID-19 infection: targeting the sigma-1 receptor |
title_fullStr | Repurposing of CNS drugs to treat COVID-19 infection: targeting the sigma-1 receptor |
title_full_unstemmed | Repurposing of CNS drugs to treat COVID-19 infection: targeting the sigma-1 receptor |
title_short | Repurposing of CNS drugs to treat COVID-19 infection: targeting the sigma-1 receptor |
title_sort | repurposing of cns drugs to treat covid-19 infection: targeting the sigma-1 receptor |
topic | Invited Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785036/ https://www.ncbi.nlm.nih.gov/pubmed/33403480 http://dx.doi.org/10.1007/s00406-020-01231-x |
work_keys_str_mv | AT hashimotokenji repurposingofcnsdrugstotreatcovid19infectiontargetingthesigma1receptor |