Murru Andrea, Manchia Mirko, Hajek Tomas, Nielsen René E, Rybakowski Janusz K, Sani Gabriele, Schulze Thomas G, Tondo Leonardo, Bauer Michael
Bipolar and Depressive Disorders Unit, IDIBAPS CIBERSAM, Hospital Clinic, Barcelona, Catalonia, Spain.
Section of Psychiatry, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.
Int J Bipolar Disord. 2020 May 20;8(1):21. doi: 10.1186/s40345-020-00191-4.
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.
自从锂被引入现代医学以来，人们就开始对其在治疗复发性情感障碍（锂仍是该疾病的一线治疗选择）以外的病症中的潜在用途进行自然主义观察。关于锂的抗病毒特性的一些证据始于20世纪70年代初，当时一些报告发现唇疱疹复发率有所降低。本综述旨在介绍关于锂抑制DNA和RNA病毒（包括冠状病毒科）能力的大部分临床前和临床证据，以及这种抗病毒活性所涉及的可能途径和机制。
尽管有大量的体外研究，但锂抗病毒活性的理论依据未能转化为能证明其抗病毒疗效的方法合理的临床研究。此外，还应探讨锂作为抗病毒药物的耐受性。事实上，锂治疗需要持续监测其血清水平，以预防急性毒性和长期副作用，最显著的是对肾脏和甲状腺的影响。然而，锂在不同组织中达到的浓度各不相同但具有生物等效性，病毒感染的解剖部位可能意味着对耐受性问题的不同、更低的关注需求，这需要加以解决。
锂在临床前水平显示出明确的抗病毒活性，但仍有待在临床环境中得到证实。此外，锂的多效作用机制可能为其作为靶向特定途径的抗病毒药物的潜在用途提供见解。
