Pleiotropic Effects of Tetracyclines in the Management of COVID-19: Emerging Perspectives

• Published in: Frontiers in pharmacology Vol. 12; p. 642822
• Main Authors: Al-Kuraishy, Hayder M, Al-Gareeb, Ali I, Alqarni, Mohammed, Cruz-Martins, Natália, El-Saber Batiha, Gaber
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 23-04-2021
• Subjects: acute respiratory distress syndrome; coronavirus disease 2019; COVID-19; Pharmacology; SARS-CoV-2; tetracyclines; COVID-19; acute respiratory distress syndrome; SARS-CoV-2; coronavirus disease 2019; tetracyclines
• ISSN: 1663-9812; 1663-9812
• DOI: 10.3389/fphar.2021.642822

Coronavirus disease 2019 (COVID-19) is a global infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Approximately 15% of severe cases require an intensive care unit (ICU) admission and mechanical ventilation due to development of acute respiratory distress syndrome (ARDS). Tetracyclines (TCs) are a group of bacteriostatic antibiotics, like tetracycline, minocycline, and doxycycline, effective against aerobic and anaerobic bacteria as well as Gram-positive and Gram-negative bacteria. Based on available evidences, TCs may be effective against coronaviruses and thus useful to treat COVID-19. Thus, this review aims to provide a brief overview on the uses of TCs for COVID-19 management. SARS-CoV-2 and other coronaviruses depend mainly on the matrix metalloproteinases (MMPs) for their proliferation, cell adhesion, and infiltration. The anti-inflammatory mechanisms of TCs are linked to different pathways. Briefly, TCs inhibit mitochondrial cytochrome c and caspase pathway with improvement of lymphopenia in early COVID-19. Specifically, minocycline is effective in reducing COVID-19-related complications, through attenuation of cytokine storm as apparent by reduction of interleukin (IL)-6, IL-1, and tumor necrosis factor (TNF)-α. Different clinical trials recommend the replacement of azithromycin by minocycline in the management of COVID-19 patients at high risk due to two main reasons: 1) minocycline does not prolong the QT interval and even inhibits ischemia-induced arrhythmia; 2) minocycline displays synergistic effect with chloroquine against SARS-CoV-2. Taken together, the data presented here show that TCs, mainly doxycycline or minocycline, may be potential partners in COVID-19 management, derived pneumonia, and related complications, such as acute lung injury (ALI) and ARDS.