{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T19:19:55Z","timestamp":1790882395462,"version":"4.1.0"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,4,23]],"date-time":"2021-04-23T00:00:00Z","timestamp":1619136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>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\u2013related complications, through attenuation of cytokine storm as apparent by reduction of interleukin (IL)-6, IL-1, and tumor necrosis factor (TNF)-\u03b1. 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.<\/jats:p>","DOI":"10.3389\/fphar.2021.642822","type":"journal-article","created":{"date-parts":[[2021,4,23]],"date-time":"2021-04-23T11:00:44Z","timestamp":1619175644000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":57,"title":["Pleiotropic Effects of Tetracyclines in the Management of COVID-19: Emerging Perspectives"],"prefix":"10.3389","volume":"12","author":[{"given":"Hayder M.","family":"Al-kuraishy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali I.","family":"Al-Gareeb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Alqarni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nat\u00e1lia","family":"Cruz-Martins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaber","family":"El-Saber Batiha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,4,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"141","DOI":"10.4103\/JMAU.JMAU_63_20","article-title":"COVID-19 and Phosphodiesterase Enzyme Type 5 Inhibitors","volume":"8","author":"Al-Kuraishy","year":"","journal-title":"J. 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