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. 2021 Apr 23;12:642822. doi: 10.3389/fphar.2021.642822

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Copyright © 2021 Al-kuraishy, Al-Gareeb, Alqarni, Cruz-Martins and El-Saber Batiha.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Pleiotropic effects of tetracycline in SARS-CoV-2 infection. Tetracycline has antiviral and anti-inflammatory effects. Antiviral effects of tetracycline are through inhibition of RNA-polymerase and serine protease dependent viral replications, and inhibition of the expression of CD26 and CD147, which are regarded as entry-point for SARS-CoV-2 with subsequent reduction in viral load. Anti-inflammatory effects of tetracycline are through inhibition of matrix metalloproteinases (MMPs), nuclear factor kappa B (NF-κB), Nod-like receptor pyrin 3 (NLRP3) inflammasome, and release of pro-inflammatory cytokines with subsequent attenuation of cytokine storm development. Taken together, both anti-inflammatory and antiviral effects of tetracycline inhibit development of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) in COVID-19.