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Review
. 2020 Dec 1:207:112739.
doi: 10.1016/j.ejmech.2020.112739. Epub 2020 Aug 19.

Azithromycin: The First Broad-spectrum Therapeutic

Anton Firth  1 , Praveen Prathapan  2
Affiliations
Review

Azithromycin: The First Broad-spectrum Therapeutic

Anton Firth et al. Eur J Med Chem. .

Abstract

The Strategic Plan for Biodefense Research by the U.S. Department of Health and Human Services demarcates the need for drugs which target multiple types of pathogens to prepare for infectious threats. Azithromycin is one such broad-spectrum therapeutic that is both included in the University of Oxford's RECOVERY and excluded from the World Health Organization's SOLIDARITY trials. Here we review azithromycin's broad antibiotic, antimalarial, antiviral pharmacology and contextualise it against a broader history as the most repositioned therapeutic of the macrolide class; we further evaluate azithromycin's clinical and socio-economic propriety for respiratory pandemics and delineate a model for its combinatorial mechanism of action against COVID-19 pneumonia.

Keywords: Azithromycin; Broad-spectrum therapeutic; COVID-19.

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Conflict of interest statement

Declaration of competing interest A. Firth compiled the research and A. Firth and P. Prathapan wrote the manuscript. The authors declare no competing financial interests.

Figures

Image 1
Graphical abstract
Fig. 1
Fig. 1
Timeline of clinical and experimental milestones on the road to establishing azithromycin’s broad-spectrum profile. Early macrolide repositioning studies yielded several successful azithromycin monotherapy trials for a range of diseases; more recent in vitro studies of azithromycin have delineated a host of pharmacological properties which continually predicate a broad-spectrum profile. [Reference(s)].
Fig. 2
Fig. 2
Pharmacological profile of azithromycin during COVID-19 pneumonia pathogenesis. A) Azithromycin prophylactically inhibits pathogenic invasion via CD147. B) As a lysosomotropic agent, azithromycin accumulates in and increases the pH of endosomes and lysosomes, impeding viral replication. C) Azithromycin augments host type I interferon (IFN) kinetics during viral infection. D) COVID-19-associated mononuclear phagocyte (MNP) compartment dysregulation, lymphopenia, neutrophil activation, and blood hypercoagulation, can be ameliorated by azithromycin. E) SARS-CoV-2 activates the inflammasome leading to aberrant release of cytokines such as IL-1β. Azithromycin, a macrolide, reduces inflammasome activity and lowers IL-1β levels. F) By reducing IL-6, IL-8, and TNF-alpha, azithromycin can antagonise COVID-19-associated cytokine release syndrome (CRS) and acute respiratory distress syndrome (ARDS).
See this image and copyright information in PMC

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