Department of Medical and Molecular Genetics, Faculty of Life Sciences and Medicine, Guy's & St Thomas' Nhs Foundation Trust and King's College London NIHR Biomedical Research Centre, London, UK.
Department of Bioscience, School of Health, Sport and Bioscience, University of East London, London, UK.
Expert Opin Investig Drugs. 2022 May;31(5):475-482. doi: 10.1080/13543784.2022.2054325. Epub 2022 Mar 23.
Drug repurposing can be a successful approach to deal with the scarcity of cost-effective therapies in situations such as the COVID-19 pandemic. Tetracyclines have previously shown efficacy in preclinical acute respiratory distress syndrome (ARDS) models and initial predictions and experimental reports suggest a direct antiviral activity against SARS-CoV2. Furthermore, a few clinical reports indicate their potential in COVID-19 patients. In addition to the scarcity and limitations of the scientific evidence, the effectiveness of tetracyclines in experimental ARDS has been proven extensively, counteracting the overt inflammatory reaction and fibrosis sequelae due to a synergic combination of pharmacological activities.
This paper discusses the scientific evidence behind the application of tetracyclines for ARDS/COVID-19.
The benefits of their multi-target pharmacology and their safety profile overcome the limitations, such as antibiotic activity and low commercial interest. Immunomodulatory tetracyclines and novel chemically modified non-antibiotic tetracyclines have therapeutic potential. Further drug repurposing studies in ARDS and severe COVID-19 are necessary.
在 COVID-19 大流行等情况下,药物再利用可能是解决成本效益疗法稀缺的一种成功方法。四环素类药物先前在临床前急性呼吸窘迫综合征(ARDS)模型中显示出疗效,初步预测和实验报告表明其对 SARS-CoV2 具有直接的抗病毒活性。此外,一些临床报告表明它们在 COVID-19 患者中的潜力。除了科学证据的稀缺性和局限性外,四环素类药物在实验性 ARDS 中的有效性已被广泛证明,由于药理学活性的协同组合,可对抗明显的炎症反应和纤维化后遗症。
本文讨论了四环素类药物在 ARDS/COVID-19 中的应用的科学依据。
其多靶点药理学的益处及其安全性克服了局限性,如抗生素活性和低商业利益。免疫调节四环素类药物和新型化学修饰的非抗生素四环素类药物具有治疗潜力。在 ARDS 和严重 COVID-19 中进行进一步的药物再利用研究是必要的。