Lithium's antiviral effects: a potential drug for CoViD-19 disease?

Bipolar disorder Coronavirus GSK-3β Inositol Virus

Journal

International journal of bipolar disorders
ISSN: 2194-7511
Titre abrégé: Int J Bipolar Disord
Pays: Germany
ID NLM: 101622983

Informations de publication

Date de publication:
20 May 2020
Historique:
received: 08 05 2020
accepted: 15 05 2020
entrez: 22 5 2020
pubmed: 22 5 2020
medline: 22 5 2020
Statut: epublish

Résumé

Since its introduction in modern medicine, naturalistic observations emerged about possible uses of lithium treatment for conditions different from recurring affective disorders, for which it is still a first-line treatment option. Some evidence about the antiviral properties of lithium began in the early 1970s, when some reports found a reduction of labial-herpetic recurrences. The present review aims to present most of the pre-clinical and clinical evidence about lithium's ability to inhibit DNA and RNA viruses, including Coronaviridae, as well as the possible pathways and mechanisms involved in such antiviral activity. Despite a broad number of in vitro studies, the rationale for the antiviral activity of lithium failed to translate into methodologically sound clinical studies demonstrating its antiviral efficacy. In addition, the tolerability of lithium as an antiviral agent should be addressed. In fact, treatment with lithium requires continuous monitoring of its serum levels in order to prevent acute toxicity and long-term side effects, most notably affecting the kidney and thyroid. Yet lithium reaches heterogeneous but bioequivalent concentrations in different tissues, and the anatomical compartment of the viral infection might underpin a different, lower need for tolerability concerns which need to be addressed. Lithium presents a clear antiviral activity demonstrated at preclinical level, but that remains to be confirmed in clinical settings. In addition, the pleiotropic mechanisms of action of lithium may provide an insight for its possible use as antiviral agent targeting specific pathways.

Sections du résumé

BACKGROUND BACKGROUND
Since its introduction in modern medicine, naturalistic observations emerged about possible uses of lithium treatment for conditions different from recurring affective disorders, for which it is still a first-line treatment option. Some evidence about the antiviral properties of lithium began in the early 1970s, when some reports found a reduction of labial-herpetic recurrences. The present review aims to present most of the pre-clinical and clinical evidence about lithium's ability to inhibit DNA and RNA viruses, including Coronaviridae, as well as the possible pathways and mechanisms involved in such antiviral activity.
MAIN BODY METHODS
Despite a broad number of in vitro studies, the rationale for the antiviral activity of lithium failed to translate into methodologically sound clinical studies demonstrating its antiviral efficacy. In addition, the tolerability of lithium as an antiviral agent should be addressed. In fact, treatment with lithium requires continuous monitoring of its serum levels in order to prevent acute toxicity and long-term side effects, most notably affecting the kidney and thyroid. Yet lithium reaches heterogeneous but bioequivalent concentrations in different tissues, and the anatomical compartment of the viral infection might underpin a different, lower need for tolerability concerns which need to be addressed.
CONCLUSIONS CONCLUSIONS
Lithium presents a clear antiviral activity demonstrated at preclinical level, but that remains to be confirmed in clinical settings. In addition, the pleiotropic mechanisms of action of lithium may provide an insight for its possible use as antiviral agent targeting specific pathways.

Identifiants

pubmed: 32435920
doi: 10.1186/s40345-020-00191-4
pii: 10.1186/s40345-020-00191-4
pmc: PMC7239605
doi:

Types de publication

Journal Article Review

Langues

eng

Pagination

21

Subventions

Organisme : We acknowledge support by the Open Access Publication Funds of the SLUB/TU Dresden.
ID : IN-1502335
Organisme : Instituto de Salud Carlos IIISubdirección General de Evaluación y Fomento de la investigación, Plan Nacional 2019-2022
ID : PI19/00672

Références

J Gen Virol. 1973 Sep;20(3):395-400
pubmed: 4126713
Eur Arch Psychiatry Clin Neurosci. 2018 Dec;268(8):749-755
pubmed: 28534186
Int J Bipolar Disord. 2020 Jan 6;8(1):1
pubmed: 31903509
Am J Psychiatry. 2020 Jan 1;177(1):76-92
pubmed: 31623458
Proc Natl Acad Sci U S A. 2008 Feb 12;105(6):2052-7
pubmed: 18250315
J Gen Virol. 1993 Aug;74 ( Pt 8):1519-25
pubmed: 8393911
Lancet Gastroenterol Hepatol. 2020 May;5(5):428-430
pubmed: 32145190
Bipolar Disord. 2019 Aug;21(5):394-409
pubmed: 31112628
Am J Psychiatry. 2013 Mar;170(3):265-74
pubmed: 23361837
Biochem Biophys Res Commun. 1989 May 15;160(3):1073-8
pubmed: 2543386
PLoS One. 2017 Aug 30;12(8):e0182547
pubmed: 28854283
ACS Chem Neurosci. 2014 Jun 18;5(6):451-8
pubmed: 24803181
Bipolar Disord. 2018 Mar;20(2):97-170
pubmed: 29536616
N Engl J Med. 1979 Oct 25;301(17):942
pubmed: 481544
Mol Psychiatry. 2015 Jun;20(6):661-70
pubmed: 25687772
Pharmacopsychiatry. 2018 Sep;51(5):200-205
pubmed: 29346806
Nature. 1983 Nov 3-9;306(5938):67-9
pubmed: 6605482
Gen Hosp Psychiatry. 2020 Jul - Aug;65:15-20
pubmed: 32361660
Mem Inst Oswaldo Cruz. 2020 Feb 27;115:e190357
pubmed: 32130369
Virologie. 1988 Apr-Jun;39(2):93-101
pubmed: 2842936
Drug Dev Res. 2016 Nov;77(7):368-373
pubmed: 27633500
N Engl J Med. 2020 Apr 30;382(18):1708-1720
pubmed: 32109013
Arch Virol. 2015 Nov;160(11):2799-805
pubmed: 26315688
Int J Bipolar Disord. 2019 Jul 22;7(1):16
pubmed: 31328245
J Cell Biol. 2005 Sep 26;170(7):1101-11
pubmed: 16186256
Biol Psychiatry. 1990 Feb 15;27(4):447-53
pubmed: 2155671
Pharmacotherapy. 1996 Nov-Dec;16(6):1070-5
pubmed: 8947995
Psychopharmacology (Berl). 2019 Oct;236(10):2909-2921
pubmed: 30756134
J Med Virol. 2017 Nov;89(11):2041-2046
pubmed: 28390158
Psychiatr Genet. 2019 Apr;29(2):29-36
pubmed: 30516584
Med Microbiol Immunol. 1980;168(2):139-48
pubmed: 6256617
Pathogens. 2019 Sep 09;8(3):
pubmed: 31505777
Biosci Trends. 2020 Mar 16;14(1):69-71
pubmed: 31996494
Pharmacopsychiatry. 2018 Sep;51(5):189-193
pubmed: 29490377
Lancet Glob Health. 2020 Apr;8(4):e452-e453
pubmed: 32199105
Arch Virol. 2015 Apr;160(4):1015-20
pubmed: 25663217
J Affect Disord. 2016 Oct;203:364-373
pubmed: 27344047
Nat Commun. 2013;4:1332
pubmed: 23299882
N Engl J Med. 2020 Jun 18;382(25):e102
pubmed: 32356626
J Affect Disord. 1996 Jun 20;39(1):7-11
pubmed: 8835648
Innov Clin Neurosci. 2018 Nov 1;15(11-12):30-32
pubmed: 30834169
Nature. 2020 Apr 29;:
pubmed: 32350436
Am J Psychiatry. 2017 Nov 1;174(11):1086-1093
pubmed: 29088928
Nat Rev Drug Discov. 2016 Jun 1;15(6):440-1
pubmed: 27245396
Bipolar Disord. 2013 Aug;15(5):496-506
pubmed: 23734877
Virulence. 2019 Dec;10(1):376-413
pubmed: 30966844
Antivir Ther. 2015;20(6):565-72
pubmed: 25560301
Expert Rev Neurother. 2016 Jun;16(6):659-70
pubmed: 27058008
Cell Signal. 2018 Apr;44:82-91
pubmed: 29331582
Science. 2020 May 22;368(6493):860-868
pubmed: 32291278
Physiol Rev. 2013 Jul;93(3):1019-137
pubmed: 23899561
Bipolar Disord. 2018 Nov;20(7):583-593
pubmed: 30221434
Eur Neuropsychopharmacol. 2017 Aug;27(8):744-750
pubmed: 28666638
AIDS. 2014 Sep 10;28(14):2157-9
pubmed: 25265080
Lancet. 1983 Jul 30;2(8344):288
pubmed: 6135115
Sci Rep. 2017 May 31;7(1):2495
pubmed: 28566716
Res Vet Sci. 2018 Jun;118:288-294
pubmed: 29547727
Mol Interv. 2004 Oct;4(5):259-72
pubmed: 15471909
Pharmacol Rev. 2013 Jan 08;65(1):105-42
pubmed: 23300133
Arch Virol. 2015 Dec;160(12):2935-43
pubmed: 26239340
Expert Opin Drug Saf. 2019 Jun;18(6):497-509
pubmed: 31059293
N Engl J Med. 2020 May 7;382(19):1851-1852
pubmed: 32187463
Avian Pathol. 2007 Apr;36(2):109-14
pubmed: 17479370
Pharmacopsychiatry. 2018 Sep;51(5):177-188
pubmed: 29672801
J Affect Disord. 2020 Mar 1;264:234-241
pubmed: 32056756
PLoS One. 2011 May 06;6(5):e18669
pubmed: 21573100
Antimicrob Agents Chemother. 1984 Apr;25(4):522-3
pubmed: 6329084
Lab Invest. 1994 Jan;70(1):29-38
pubmed: 8302016
Microb Pathog. 2016 Apr;93:152-7
pubmed: 26835657
Pathobiology. 1993;61(3-4):216-21
pubmed: 8216844
Nature. 2020 Jun;582(7811):289-293
pubmed: 32272481
Lancet. 1983 Aug 27;2(8348):516
pubmed: 6136673
J Affect Disord. 1998 Jan;47(1-3):177-82
pubmed: 9476758
N Engl J Med. 2020 Jun 11;382(24):2327-2336
pubmed: 32275812
Future Neurol. 2016 May;11(2):135-148
pubmed: 29339929
Br J Psychiatry. 1974 Mar;124(0):273-9
pubmed: 4365487
ACS Chem Neurosci. 2014 Jun 18;5(6):434-42
pubmed: 24738557
J Virol. 1970 Feb;5(2):173-8
pubmed: 4988267
World Psychiatry. 2015 Oct;14(3):339-47
pubmed: 26407790
Elife. 2018 May 31;7:
pubmed: 29848441
Avian Pathol. 2009 Jun;38(3):215-21
pubmed: 19468938

Auteurs

Andrea Murru (A)

Bipolar and Depressive Disorders Unit, IDIBAPS CIBERSAM, Hospital Clinic, Barcelona, Catalonia, Spain.

Mirko Manchia (M)

Section of Psychiatry, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.
Unit of Clinical Psychiatry, University Hospital Agency of Cagliari, Cagliari, Italy.
Department of Pharmacology, Dalhousie University, Halifax, NS, Canada.

Tomas Hajek (T)

Department of Psychiatry, Dalhousie University, Halifax, NS, Canada.

René E Nielsen (RE)

Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
Psychiatry-Aalborg University Hospital, Aalborg, Denmark.

Janusz K Rybakowski (JK)

Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznan, Poland.
Department of Psychiatric Nursing, Poznan University of Medical Sciences, Poznan, Poland.

Gabriele Sani (G)

Department of Neuroscience, Section of Psychiatry, Università Cattolica del Sacro Cuore, Rome, Italy.
Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.

Thomas G Schulze (TG)

Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Munich, Germany.
Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, NY, USA.
Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August University Göttingen, Göttingen, Germany.
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA.
Department of Genetic Epidemiology, Central Institute of Mental Health, Mannheim, Germany.

Leonardo Tondo (L)

International Consortium for Research on Mood & Psychotic Disorders, McLean Hospital, Belmont, MA, USA.
Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
Lucio Bini Mood Disorders Centers, Cagliari and Rome, Italy.

Michael Bauer (M)

Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany. michael.bauer@uniklinikum-dresden.de.

Classifications MeSH