Reply to: How Many SARS-CoV-2 “Viroporins” Are Really Ion Channels?

Toft-Bertelsen, Trine L.; Jeppesen, Mads Gravers; Landbrug, Asante; Mujezinovic, Amer; Bentzen, Bo Hjorth; Kledal, Thomas N.

doi:10.1038/s42003-022-03670-9

Cited by 3 publications

(2 citation statements)

References 9 publications

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“…Miller and his colleagues also solved a series of cryo-EM structures of ORF3a dimers that unlikely represent membrane proteins permeable to K + or other cations. It has been suggested that the small ionic currents previously detected in Xenopus oocytes injected with ORF3a [ 5 , 8 ] could be attributed to endogenous calcium activated chloride channel [ 43 , 45 , 46 ]. Thereby, we propose, as [ 43 ] also do, that ORF3a at the cell surface is not an ion channel.…”

Section: Discussionmentioning

confidence: 99%

Some aspects of the life of SARS-CoV-2 ORF3a protein in mammalian cells

Jiao,

Miranda,

et al. 2023

Heliyon

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Section: Discussionmentioning

confidence: 99%

Some aspects of the life of SARS-CoV-2 ORF3a protein in mammalian cells

Jiao,

Miranda,

et al. 2023

Heliyon

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“…Amantadine, given to patients with Multiple Sclerosis (MS) and Parkinson´s Disease (PD) for improvement of fatigue and treatment of levodopa dyskinesia, respectively, seems to reduce the risk of SARS-CoV-2 infection [ [3] , [4] , [5] , [6] ]. The underlying mechanism could be that amantadine inhibits replication and/or virulence of SARS-CoV-2 [ 7 , 8 ] and blocks the ion channel activity of Protein E and ORF10 from SARS-CoV-2 in vitro [ 9 , 10 ] . In support of this, in vitro studies have shown that amantadine blocks ion channel activity of Protein E from the closely related SARS-CoV-1 and that this viroporin is central for virus-mediated lung pathology in mice [ [11] , [12] , [13] ].…”

Section: Introductionmentioning

confidence: 99%

Amantadine for COVID-19 treatment (ACT) study: a randomized, double-blinded, placebo-controlled clinical trial

Weis,

Bollerup,

Sund

et al. 2023

Clinical Microbiology and Infection

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Advancing the field of viroporins—Structure, function and pharmacology: IUPHAR Review 39

Devantier,

Kjær,

Griffin

et al. 2024

British J Pharmacology

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Viroporins possess important potential as antiviral targets due to their critical roles during virus life cycles, spanning from virus entry to egress. Although the antiviral amantadine targets the M2 viroporin of influenza A virus, successful progression of other viroporin inhibitors into clinical use remains challenging. These challenges relate in varying proportions to a lack of reliable full‐length 3D‐structures, difficulties in functionally characterising individual viroporins, and absence of verifiable direct binding between inhibitor and viroporin. This review offers perspectives to help overcome these challenges. We provide a comprehensive overview of the viroporin family, including their structural and functional features, highlighting the moldability of their energy landscapes and actions. To advance the field, we suggest a list of best practices to aspire towards unambiguous viroporin identification and characterisation, along with considerations of potential pitfalls. Finally, we present current and future scenarios of, and prospects for, viroporin targeting drugs.

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Reply to: How Many SARS-CoV-2 “Viroporins” Are Really Ion Channels?

Cited by 3 publications

References 9 publications

Some aspects of the life of SARS-CoV-2 ORF3a protein in mammalian cells

Some aspects of the life of SARS-CoV-2 ORF3a protein in mammalian cells

Amantadine for COVID-19 treatment (ACT) study: a randomized, double-blinded, placebo-controlled clinical trial

Advancing the field of viroporins—Structure, function and pharmacology: IUPHAR Review 39

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