Repurposing of CNS drugs to treat COVID-19 infection: targeting the sigma-1 receptor

Hashimoto, Kenji

doi:10.1007/s00406-020-01231-x

Cited by 101 publications

(127 citation statements)

References 91 publications

Supporting

Mentioning

121

Contrasting

Unclassified

Order By: Relevance

“…Sigma ligands has recently been explored as a therapeutic target in COVID-19 repurposing therapy ( Abate et al, 2020 ; Vela, 2020 ; Hashimoto, 2021 ). Both Sigmar1 agonist (fluvoxamine) ( Lenze et al, 2020 ) and antagonist (haloperidol) ( Hoertel et al, 2021 ) underwent clinical trial for possible therapy in patients with COVID-19.…”

Section: Physiological and Pathological Role Of Sigmar1mentioning

confidence: 99%

Sigmar1’s Molecular, Cellular, and Biological Functions in Regulating Cellular Pathophysiology

et al. 2021

View full text Add to dashboard Cite

The Sigma 1 receptor (Sigmar1) is a ubiquitously expressed multifunctional inter-organelle signaling chaperone protein playing a diverse role in cellular survival. Recessive mutation in Sigmar1 have been identified as a causative gene for neuronal and neuromuscular disorder. Since the discovery over 40 years ago, Sigmar1 has been shown to contribute to numerous cellular functions, including ion channel regulation, protein quality control, endoplasmic reticulum-mitochondrial communication, lipid metabolism, mitochondrial function, autophagy activation, and involved in cellular survival. Alterations in Sigmar1’s subcellular localization, expression, and signaling has been implicated in the progression of a wide range of diseases, such as neurodegenerative diseases, ischemic brain injury, cardiovascular diseases, diabetic retinopathy, cancer, and drug addiction. The goal of this review is to summarize the current knowledge of Sigmar1 biology focusing the recent discoveries on Sigmar1’s molecular, cellular, pathophysiological, and biological functions.

show abstract

Section: Physiological and Pathological Role Of Sigmar1mentioning

confidence: 99%

Sigmar1’s Molecular, Cellular, and Biological Functions in Regulating Cellular Pathophysiology

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Foremost amongst these is a generic selective serotonin reuptake inhibitor (SSRI) fluvoxamine, that has been shown to protect against severe COVID-19 in a Phase 2 trial 8 as well as a real-world study 9 and is currently undergoing a Phase 3 study 10 . The suggested protective effect of fluvoxamine has been tentatively linked to modulation of immune response through activation of the ER stress and sigma receptor 11 , or blockade of acid sphingomyelinase 7,12,13 , however the underlying cell biological mechanism remains unknown.…”

Section: Main Textmentioning

confidence: 99%

Low-dose fluvoxamine modulates endocytic trafficking of SARS-CoV-2 spike protein: a potential mechanism for anti-COVID-19 protection by antidepressants

Glebov

2021

Preprint

View full text Add to dashboard Cite

Commonly prescribed antidepressants may be associated with protection against severe COVID-19, with one drug (fluvoxamine) currently undergoing a Phase 3 clinical trial. The mechanism of their action, however, remains unknown. Here, I investigated the effect of fluvoxamine on membrane trafficking of the SARS-CoV-2 spike protein and its cell host receptor ACE2 in HEK293T cells. A sub-therapeutic concentration (80 nM) of fluvoxamine rapidly upregulated fluid-phase endocytosis, resulting in enhanced accumulation of the spike-ACE2 complex in enlarged early endosomes. Diversion of endosomal trafficking provides a simple cell biological mechanism consistent with the protective effect of antidepressants against COVID-19, highlighting their therapeutic and prophylactic potential.

show abstract

“…This screen showed that the Sigma-2 receptor (part of a family of proteins implicated in viral infection) 242 interacts with the CoVID-19 ORF9c. Knockout of Sigma-2 receptor reduces SARS-CoV-2 replication, 243 indicating that modulation of this protein may help treat CoVID-19 patients. In retrospect, two issues stand in the way of this logic.…”

Section: Targeting Transcription: Remdesivirmentioning

confidence: 99%

Science’s Response to COVID-19

Aye¹,

Long²

2021

Preprint

View full text Add to dashboard Cite

CoVID-19 is a multi-symptomatic disease which has made a global impact due to its ability to spread rapidly, and its relatively high mortality rate. Beyond the heroic efforts to develop vaccines, which we will not discuss, the response of scientists and clinicians to this complex problem has reflected the need to detect CoVID-19 rapidly, to diagnose patients likely to show adverse symptoms, and to treat severe and critical CoVID-19. Here we aim to encapsulate these varied and sometimes conflicting approaches and the resulting data in terms of chemistry and biology. In the process we highlight emerging concepts, and potential future applications that may arise out of this immense effort.

show abstract

Repurposing of CNS drugs to treat COVID-19 infection: targeting the sigma-1 receptor

Cited by 101 publications

References 91 publications

Sigmar1’s Molecular, Cellular, and Biological Functions in Regulating Cellular Pathophysiology

Sigmar1’s Molecular, Cellular, and Biological Functions in Regulating Cellular Pathophysiology

Low-dose fluvoxamine modulates endocytic trafficking of SARS-CoV-2 spike protein: a potential mechanism for anti-COVID-19 protection by antidepressants

Science’s Response to COVID-19

Contact Info

Product

Resources

About