PB28, the Sigma-1 and Sigma-2 Receptors Modulator With Potent Anti–SARS-CoV-2 Activity: A Review About Its Pharmacological Properties and Structure Affinity Relationships

Abate, Carmen; Niso, Mauro; Abatematteo, Francesca Serena; Contino, Marialessandra; Colabufo, Nicola Antonio; Berardi, Francesco

doi:10.3389/fphar.2020.589810

Cited by 23 publications

(23 citation statements)

References 80 publications

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“…Despite the σ 1 R/σ 2 R mixed profile of PB28, this cyclohexylpiperazine derivative emerged as one of the most potent putative σ 1 R antagonist/σ 2 R agonist known until today, and as we will discuss in the next section, it has been extensively studied both for its biological activity and the SAfiRs as a lead compound. 160 Interestingly, PB28 has been recently tested for its in vitro anti-SARS-CoV-2 activity, and it was found to be more potent and less cardiotoxic than hydroxychloroquine, supporting further studies as a promising pan-viral candidate. 161 …”

Section: σR Ligands With Cytotoxic Effectsmentioning

confidence: 96%

Recent Advances in the Development of Sigma Receptor Ligands as Cytotoxic Agents: A Medicinal Chemistry Perspective

et al. 2021

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Since their discovery as distinct receptor proteins, the specific physiopathological role of sigma receptors (σRs) has been deeply investigated. It has been reported that these proteins, classified into two subtypes indicated as σ 1 and σ 2 , might play a pivotal role in cancer growth, cell proliferation, and tumor aggressiveness. As a result, the development of selective σR ligands with potential antitumor properties attracted significant attention as an emerging theme in cancer research. This perspective deals with the recent advances of σR ligands as novel cytotoxic agents, covering articles published between 2010 and 2020. An up-to-date description of the medicinal chemistry of selective σ 1 R and σ 2 R ligands with antiproliferative and cytotoxic activities has been provided, including major pharmacophore models and comprehensive structure–activity relationships for each main class of σR ligands.

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Section: σR Ligands With Cytotoxic Effectsmentioning

confidence: 96%

Recent Advances in the Development of Sigma Receptor Ligands as Cytotoxic Agents: A Medicinal Chemistry Perspective

et al. 2021

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“…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

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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.

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“…PB28 has been identified as a drug that can lessen the severity of SARS-CoV-2 infection [ 61 ]. PB28 has been reviewed in much detail regarding its role in preventing the severity of SARS-CoV-2 infection [ 133 ]. One compelling hypothesis that could explain PB28’s SARS-CoV-2 protective properties involves the InsP 3 receptor and the SARS-CoV-2 NSP6 protein.…”

Section: Sigma Receptor Drugs and Sars-cov-2mentioning

confidence: 99%

Drugs that offer the potential to reduce hospitalization and mortality from SARS-CoV-2 infection: The possible role of the sigma-1 receptor and autophagy

Brimson

Prasanth

Malar

et al. 2021

Expert Opinion on Therapeutic Targets

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Introduction: Despite the availability of new vaccines for SARS-CoV-2, there has been slow uptake and problems with supply in some parts of the world. Hence, there is still a necessity for drugs that can prevent hospitalization of patients and reduce the strain on health care systems. Drugs with sigma affinity potentially provide protection against the most severe symptoms of SARS-COV-2 and could prevent mortality via interactions with the sigma-1 receptor. Areas covered: This review examines the role of the sigma-1 receptor and autophagy in SARS-CoV-2 infections and how they may be linked. The authors reveal how sigma ligands may reduce the symptoms, complications, and deaths resulting from SARS-CoV-2 and offer insights on those patient cohorts that may benefit most from these drugs. Expert opinion: Drugs with sigma affinity potentially offer protection against the most severe symptoms of SARS-CoV-2 via interactions with the sigma-1 receptor. Agonists of the sigma-1 receptor may provide protection of the mitochondria, activate mitophagy to remove damaged and leaking mitochondria, prevent ER stress, manage calcium ion transport, and induce autophagy to prevent cell death in response to infection.

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PB28, the Sigma-1 and Sigma-2 Receptors Modulator With Potent Anti–SARS-CoV-2 Activity: A Review About Its Pharmacological Properties and Structure Affinity Relationships

Cited by 23 publications

References 80 publications

Recent Advances in the Development of Sigma Receptor Ligands as Cytotoxic Agents: A Medicinal Chemistry Perspective

Recent Advances in the Development of Sigma Receptor Ligands as Cytotoxic Agents: A Medicinal Chemistry Perspective

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

Drugs that offer the potential to reduce hospitalization and mortality from SARS-CoV-2 infection: The possible role of the sigma-1 receptor and autophagy

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