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  1. Article ; Online: Prominent Efficacy of Amantadine against Human Borna Disease Virus Infection In Vitro and In Vivo. Comment on Fink et al. Amantadine Inhibits SARS-CoV-2 In Vitro.

    Bode, Liv / Dietrich, Detlef E / Spannhuth, Carsten W / Ludwig, Hanns

    Viruses

    2022  Volume 14, Issue 3

    Abstract: Amantadine (1-amino-adamantane) is a versatile antiviral compound which has been licensed for decades against influenza viruses. During the Corona pandemic, its effect to inhibit SARS-CoV-2 in vitro has been investigated. However, an in vivo oral ... ...

    Abstract Amantadine (1-amino-adamantane) is a versatile antiviral compound which has been licensed for decades against influenza viruses. During the Corona pandemic, its effect to inhibit SARS-CoV-2 in vitro has been investigated. However, an in vivo oral inapplicability was concluded due to ID
    MeSH term(s) Amantadine/pharmacology ; Animals ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Borna disease virus ; COVID-19/drug therapy ; Humans ; SARS-CoV-2
    Chemical Substances Antiviral Agents ; Amantadine (BF4C9Z1J53)
    Language English
    Publishing date 2022-02-28
    Publishing country Switzerland
    Document type Journal Article ; Comment
    ZDB-ID 2516098-9
    ISSN 1999-4915 ; 1999-4915
    ISSN (online) 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v14030494
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Prominent Efficacy of Amantadine against Human Borna Disease Virus Infection In Vitro and In Vivo. Comment on Fink et al. Amantadine Inhibits SARS-CoV-2 In Vitro. Viruses 2021, 13, 539

    Bode, Liv / Dietrich, Detlef E. / Spannhuth, Carsten W. / Ludwig, Hanns

    Viruses. 2022 Feb. 28, v. 14, no. 3

    2022  

    Abstract: Amantadine (1-amino-adamantane) is a versatile antiviral compound which has been licensed for decades against influenza viruses. During the Corona pandemic, its effect to inhibit SARS-CoV-2 in vitro has been investigated. However, an in vivo oral ... ...

    Abstract Amantadine (1-amino-adamantane) is a versatile antiviral compound which has been licensed for decades against influenza viruses. During the Corona pandemic, its effect to inhibit SARS-CoV-2 in vitro has been investigated. However, an in vivo oral inapplicability was concluded due to ID₅₀ doses exceeding eight times the estimated maximum tolerable plasma levels reached by 600 mg orally daily. In contrast, amantadine has been shown to be extraordinarily efficient against human neurotropic Borna disease virus (BoDV-1), presenting with both anti-depressive and anti-viral efficacy against a placebo, achieved by a well-tolerated low oral daily dose of 200 mg amantadine.
    Keywords Borna disease virus ; Severe acute respiratory syndrome coronavirus 2 ; antiviral agents ; humans ; influenza ; pandemic ; placebos
    Language English
    Dates of publication 2022-0228
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article
    ZDB-ID 2516098-9
    ISSN 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v14030494
    Database NAL-Catalogue (AGRICOLA)

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  3. Article ; Online: Antiviral treatment perspective against Borna disease virus 1 infection in major depression: a double-blind placebo-controlled randomized clinical trial.

    Dietrich, Detlef E / Bode, Liv / Spannhuth, Carsten W / Hecker, Hartmut / Ludwig, Hanns / Emrich, Hinderk M

    BMC pharmacology & toxicology

    2020  Volume 21, Issue 1, Page(s) 12

    Abstract: Background: Whether Borna disease virus (BDV-1) is a human pathogen remained controversial until recent encephalitis cases showed BDV-1 infection could even be deadly. This called to mind previous evidence for an infectious contribution of BDV-1 to ... ...

    Abstract Background: Whether Borna disease virus (BDV-1) is a human pathogen remained controversial until recent encephalitis cases showed BDV-1 infection could even be deadly. This called to mind previous evidence for an infectious contribution of BDV-1 to mental disorders. Pilot open trials suggested that BDV-1 infected depressed patients benefitted from antiviral therapy with a licensed drug (amantadine) which also tested sensitive in vitro. Here, we designed a double-blind placebo-controlled randomized clinical trial (RCT) which cross-linked depression and BDV-1 infection, addressing both the antidepressant and antiviral efficacy of amantadine.
    Methods: The interventional phase II RCT (two 7-weeks-treatment periods and a 12-months follow-up) at the Hannover Medical School (MHH), Germany, assigned currently depressed BDV-1 infected patients with either major depression (MD; N = 23) or bipolar disorder (BD; N = 13) to amantadine sulphate (PK-Merz®; twice 100 mg orally daily) or placebo treatment, and contrariwise, respectively. Clinical changes were assessed every 2-3 weeks by the 21-item Hamilton rating scale for depression (HAMD) (total, single, and combined scores). BDV-1 activity was determined accordingly in blood plasma by enzyme immune assays for antigens (PAG), antibodies (AB) and circulating immune complexes (CIC).
    Results: Primary outcomes (≥25% HAMD reduction, week 7) were 81.3% amantadine vs. 35.3% placebo responder (p = 0.003), a large clinical effect size (ES; Cohen's d) of 1.046, and excellent drug tolerance. Amantadine was safe reducing suicidal behaviour in the first 2 weeks. Pre-treatment maximum infection levels were predictive of clinical improvement (AB, p = 0.001; PAG, p = 0.026; HAMD week 7). Respective PAG and CIC levels correlated with AB reduction (p = 0,001 and p = 0.034, respectively). Follow-up benefits (12 months) correlated with dropped cumulative infection measures over time (p < 0.001). In vitro, amantadine concentrations as low as 2.4-10 ng/mL (50% infection-inhibitory dose) prevented infection with human BDV Hu-H1, while closely related memantine failed up to 100,000-fold higher concentration (200 μg/mL).
    Conclusions: Our findings indicate profound antidepressant efficacy of safe oral amantadine treatment, paralleling antiviral effects at various infection levels. This not only supports the paradigm of a link of BDV-1 infection and depression. It provides a novel possibly practice-changing low cost mental health care perspective for depressed BDV-1-infected patients addressing global needs.
    Trial registration: The trial was retrospectively registered in the German Clinical Trials Registry on 04th of March 2015. The trial ID is DRKS00007649; https://www.drks.de/drks_web/setLocale_EN.do.
    MeSH term(s) Adult ; Amantadine/pharmacology ; Amantadine/therapeutic use ; Animals ; Antibodies, Viral/blood ; Antidepressive Agents/pharmacology ; Antidepressive Agents/therapeutic use ; Antigens, Viral/blood ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Bipolar Disorder/drug therapy ; Borna Disease/drug therapy ; Borna Disease/virology ; Borna disease virus/drug effects ; Borna disease virus/physiology ; Cells, Cultured ; Cross-Over Studies ; Depressive Disorder, Major/drug therapy ; Double-Blind Method ; Female ; Humans ; Male ; Middle Aged ; Rabbits ; Virus Replication/drug effects
    Chemical Substances Antibodies, Viral ; Antidepressive Agents ; Antigens, Viral ; Antiviral Agents ; Amantadine (BF4C9Z1J53)
    Keywords covid19
    Language English
    Publishing date 2020-02-17
    Publishing country England
    Document type Clinical Trial, Phase II ; Journal Article ; Randomized Controlled Trial
    ZDB-ID 2680259-4
    ISSN 2050-6511 ; 2050-6511
    ISSN (online) 2050-6511
    ISSN 2050-6511
    DOI 10.1186/s40360-020-0391-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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