Safety and Efficacy of Amiodarone in a Patient With COVID-19

Castaldo, Nadia; Aimo, Alberto; Castiglione, Vincenzo; Padalino, C.; Emdin, Michele; Tascini, Carlo

doi:10.1016/j.jaccas.2020.04.053

Cited by 16 publications

(17 citation statements)

References 10 publications

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“…Unfortunately, the study was not a formal clinical trial, and the statistical significance of this result is not known ( Turone, 2014 ; Gupta-Wright et al, 2015 ). Recently, the case of a patient affected by COVID-19-related respiratory failure who recovered after only supportive measures and off-label short therapy with amiodarone (starting on the second day from admission and lasting 5 days; administered on day 1 as a 15 mg/kg/24 h intravenous infusion, followed by oral administration of 400 mg twice daily) has been reported ( Castaldo et al, 2020 ). Accordingly, amiodarone, widely prescribed to treat both ventricular and supraventricular arrhythmias, has been proposed as a possible therapy (alone or as part of a combination regimen) to prevent SARS-CoV-2 infection rather than to treat symptomatic or severe COVID-19 patients ( Aimo et al, 2020 ; Sanchis-Gomar et al, 2020 ).…”

Section: Sigma-1 Receptor Ligands Exert Antiviral Activitymentioning

confidence: 99%

Repurposing Sigma-1 Receptor Ligands for COVID-19 Therapy?

Vela

2020

Front. Pharmacol.

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Outbreaks of emerging infections, such as COVID-19 pandemic especially, confront health professionals with the unique challenge of treating patients. With no time to discover new drugs, repurposing of approved drugs or in clinical development is likely the only solution. Replication of coronaviruses (CoVs) occurs in a modified membranous compartment derived from the endoplasmic reticulum (ER), causes host cell ER stress and activates pathways to facilitate adaptation of the host cell machinery to viral needs. Accordingly, modulation of ER remodeling and ER stress response might be pivotal in elucidating CoV-host interactions and provide a rationale for new therapeutic, host-based antiviral approaches. The sigma-1 receptor (Sig-1R) is a ligand-operated, ER membrane-bound chaperone that acts as an upstream modulator of ER stress and thus a candidate host protein for host-based repurposing approaches to treat COVID-19 patients. Sig-1R ligands are frequently identified in in vitro drug repurposing screens aiming to identify antiviral compounds against CoVs, including severe acute respiratory syndrome CoV-2 (SARS-CoV-2). Sig-1R regulates key mechanisms of the adaptive host cell stress response and takes part in early steps of viral replication. It is enriched in lipid rafts and detergent-resistant ER membranes, where it colocalizes with viral replicase proteins. Indeed, the non-structural SARS-CoV-2 protein Nsp6 interacts with Sig-1R. The activity of Sig-1R ligands against COVID-19 remains to be specifically assessed in clinical trials. This review provides a rationale for targeting Sig-1R as a host-based drug repurposing approach to treat COVID-19 patients. Evidence gained using Sig-1R ligands in unbiased in vitro antiviral drug screens and the potential mechanisms underlying the modulatory effect of Sig-1R on the host cell response are discussed. Targeting Sig-1R is not expected to reduce dramatically established viral replication, but it might interfere with early steps of virus-induced host cell reprogramming, aid to slow down the course of infection, prevent the aggravation of the disease and/or allow a time window to mature a protective immune response. Sig-1R-based medicines could provide benefit not only as early intervention, preventive but also as adjuvant therapy.

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Section: Sigma-1 Receptor Ligands Exert Antiviral Activitymentioning

confidence: 99%

Repurposing Sigma-1 Receptor Ligands for COVID-19 Therapy?

Vela

2020

Front. Pharmacol.

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“…Among the 231 articles (PubMed and Google Scholar), 91 were retained [ 3 , 12 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 ,…”

Section: Update (16 June 2021) On Studies With Fiasmas In the Sars-cov-2 Infectionmentioning

confidence: 99%

Update on Functional Inhibitors of Acid Sphingomyelinase (FIASMAs) in SARS-CoV-2 Infection

Loas

Corre

2021

Pharmaceuticals

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The SARS-CoV-2 outbreak is characterized by the need of the search for curative drugs for treatment. In this paper, we present an update of knowledge about the interest of the functional inhibitors of acid sphingomyelinase (FIASMAs) in SARS-CoV-2 infection. Forty-nine FIASMAs have been suggested in the treatment of SARS-CoV-2 infection using in silico, in vitro or in vivo studies. Further studies using large-sized, randomized and double-blinded controlled clinical trials are needed to evaluate FIASMAs in SARS-CoV-2 infection as off-label therapy.

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“…Past studies showed that amiodarone has in vitro antiviral activity against SARS-CoV by interfering with endocytosis and viral replication [49,50]. It is currently being studied in clinical trials against COVID-19 [51] and it was recently documented in a case report to successfully treat COVID-19 [52]. In summary, COKE successfully highlighted compounds shown to be active against SARS-CoV-2 in the phenotypic assay.…”

Section: Comparison Of the Drug-target Associations In The Coke Datasmentioning

confidence: 99%

COVID-19 Knowledge Extractor (COKE): A Tool and a Web Portal to Extract Drug - Target Protein Associations from the CORD-19 Corpus of Scientific Publications on COVID-19

Korn¹,

Pervitsky²,

Bobrowski³

et al. 2020

Preprint

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Objective: The COVID-19 pandemic has catalyzed a widespread effort to identify drug candidates and biological targets of relevance to SARS-COV-2 infection, which resulted in large numbers of publications on this subject. We have built the COVID-19 Knowledge Extractor (COKE), a web application to extract, curate, and annotate essential drug-target relationships from the research literature on COVID-19 to assist drug repurposing efforts. Materials and Methods: SciBiteAI ontological tagging of the COVID Open Research Dataset (CORD-19), a repository of COVID-19 scientific publications, was employed to identify drug-target relationships. Entity identifiers were resolved through lookup routines using UniProt and DrugBank. A custom algorithm was used to identify co-occurrences of protein and drug terms, and confidence scores were calculated for each entity pair. Results: COKE processing of the current CORD-19 database identified about 3,000 drug-protein pairs, including 29 unique proteins and 500 investigational, experimental, and approved drugs. Some of these drugs are presently undergoing clinical trials for COVID-19. Discussion: The rapidly evolving situation concerning the COVID-19 pandemic has resulted in a dramatic growth of publications on this subject in a short period. These circumstances call for methods that can condense the literature into the key concepts and relationships necessary for insights into SARS-CoV-2 drug repurposing. Conclusion: The COKE repository and web application deliver key drug - target protein relationships to researchers studying SARS-CoV-2. COKE portal may provide comprehensive and critical information on studies concerning drug repurposing against COVID-19. COKE is freely available at <a href="https://coke.mml.unc.edu/">https://coke.mml.unc.edu/</a> and the code is available at <a href="https://github.com/DnlRKorn/CoKE">https://github.com/DnlRKorn/CoKE</a>.

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Safety and Efficacy of Amiodarone in a Patient With COVID-19

Cited by 16 publications

References 10 publications

Repurposing Sigma-1 Receptor Ligands for COVID-19 Therapy?

Repurposing Sigma-1 Receptor Ligands for COVID-19 Therapy?

Update on Functional Inhibitors of Acid Sphingomyelinase (FIASMAs) in SARS-CoV-2 Infection

COVID-19 Knowledge Extractor (COKE): A Tool and a Web Portal to Extract Drug - Target Protein Associations from the CORD-19 Corpus of Scientific Publications on COVID-19

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