Azithromycin through the Lens of the COVID-19 Treatment

Abstract

Azithromycin has become famous in the last two years, not for its main antimicrobial effect, but for its potential use as a therapeutic agent for COVID-19 infection. Initially, there were some promising results that supported its use, but it has become clear that scientific results are insufficient to support such a positive assessment. In this review we will present all the literature data concerning the activity of azithromycin as an antimicrobial, an anti-inflammatory, or an antivirus agent. Our aim is to conclude whether its selection should remain as a valuable antivirus agent or if its use simply has an indirect therapeutic contribution due to its antimicrobial and/or immunomodulatory activity, and therefore, if its further use for COVID-19 treatment should be interrupted. This halt will prevent further antibiotic resistance expansion and will keep azithromycin as a valuable anti-infective therapeutic agent.

Keywords: COVID-19; antivirus; azithromycin; coronavirus; immunolides; macrolides; virus.

Figure 1

Molecular structure of the mother macrolide molecule erythromycin and its semisynthetic derivatives azithromycin (15-membered) and clarithromycin (14-membered). Blue and red colors in the structures represent modifications of the mother molecule (black).

Figure 2

Structure of azithromycin in complex with the 70S ribosome carrying A-, P-, and E-site tRNAs. (A,B) Location of the ribosome-bound azithromycin (yellow) in the macrolide binding pocket at the entrance to the nascent peptide exit tunnel (NPET) of the 70S ribosome relative to tRNAs viewed as cross-cut sections through the ribosome. The 30S subunit is shown in light yellow, the 50S subunit is in light blue, the mRNA is in magenta, and the A-, P-, and E-site tRNAs are colored green, dark blue, and orange, respectively. The phenylalanyl and formyl-methionyl moieties of the A- and P-site tRNAs are shown as spheres [15].

Figure 3

Immunomodulatory effects of azithromycin.