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Repurposing of CNS drugs to treat COVID-19 infection: targeting the sigma-1 receptor.
Hashimoto, Kenji.
  • Hashimoto K; Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, 1-8-1 Inohana, Chiba, 260-8670, Japan. hashimoto@faculty.chiba-u.jp.
Eur Arch Psychiatry Clin Neurosci ; 271(2): 249-258, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1009130
ABSTRACT
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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Full text: Available Collection: International databases Database: MEDLINE Main subject: Central Nervous System Agents / Receptors, sigma / Drug Repositioning / COVID-19 Drug Treatment Type of study: Prognostic study / Randomized controlled trials Limits: Animals / Humans Language: English Journal: Eur Arch Psychiatry Clin Neurosci Journal subject: Neurology / Psychiatry Year: 2021 Document Type: Article Affiliation country: S00406-020-01231-x

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Central Nervous System Agents / Receptors, sigma / Drug Repositioning / COVID-19 Drug Treatment Type of study: Prognostic study / Randomized controlled trials Limits: Animals / Humans Language: English Journal: Eur Arch Psychiatry Clin Neurosci Journal subject: Neurology / Psychiatry Year: 2021 Document Type: Article Affiliation country: S00406-020-01231-x