Clinical evidences on the antiviral properties of macrolide antibiotics in the COVID-19 era and beyond

Abstract

Macrolides are a large group of antibiotics characterised by the presence of a macro-lactone ring of variable size. The prototype of macrolide antibiotics, erythromycin was first produced by Streptomyces and associated species more than half a century ago; other related drugs were developed. These drugs have been shown to have several pharmacological properties: in addition to their antibiotic activity, they possess some anti-inflammatory properties and have been also considered against non-bacterial infections. In this review, we analysed the available clinical evidences regarding the potential anti-viral activity of macrolides, by focusing on erythromycin, clarithromycin and azithromycin. Overall, there is no significant evidences so far that macrolides might have a direct benefit on most of viral infections considered in this review (RSV, Influenza, coronaviruses, Ebola and Zika viruses). However, their clinical benefit cannot be ruled out without further and focused clinical studies. Macrolides may improve the clinical course of viral respiratory infections somehow, at least through indirect mechanisms relying on some and variable anti-inflammatory and/or immunomodulatory effects, in addition to their well-known antibacterial activity.

COVID-19 Pneumonia in Children: From Etiology to Management

“…-Antibiotics: Their use is discouraged unless there are signs of bacterial co-infection. The usefulness of macrolides, especially azithromycin, for their anti-inflammatory properties is also questionable (19,52,60,66). -Corticosteroids: Their routine use is discouraged; however, they should be considered in cases of PARDS, secondary haemophagocytic lymphoistiocytosis, septic shock, or concomitant asthma.…”

“…- Antibiotics: Their use is discouraged unless there are signs of bacterial co-infection. The usefulness of macrolides, especially azithromycin, for their anti-inflammatory properties is also questionable ( 19 , 52 , 60 , 66 ).…”

AI drug discovery screening for COVID-19 reveals zafirlukast as a repurposing candidate

“…The results based on the manually curated version of the same dataset, after adding the known SARS-CoV-2 3CLpro inhibitors to the training set, show below zafirlukast also the following interesting, high ranked candidates: an example of beta-lactam antibiotic, ampicillin, as well as macrolide antibiotics, erythromycin and clarithromycin. The macrolides are supposed to improve the course of viral infections, at least through indirect mechanisms including anti-inflammatory and/or immunomodulatory effects; however, there is no clear evidence of clinical efficacy of macrolides in coronaviruses infections [ 50 ]. Also, a representation of antiviral drugs from the group of inhibitors of DNA polimerases, consisting of valacyclovir, ganciclovir, and its prodrug valganciclovir, was observed.…”

How glycobiology can help us treat and beat the COVID-19 pandemic

“…Macrolides are molecules with a large macrocyclic lactone ring to which one or two deoxy sugars may be attached. Macrolide antibiotics did not show clinical evidence for antiviral properties on SARS-CoV-2 infection ( 88 ), and Azithromycin did not improve clinical outcome when used together with Hydroxychloroquine ( 89 ). Ivermectin (an anti-parasitic macrolide) revealed broad-spectrum antiviral activity ( 90 ), also evidenced against SARS-CoV-2 in in vitro assays ( 91 ) ( Table 1 and Figure 5 ).…”