Role of azithromycin in antiviral treatment: enhancement of interferon-dependent antiviral pathways and mitigation of inflammation may rely on inhibition of the MAPK cascade?

Azithromycin is a macrolide-type antibiotic used against a broad range of bacterial infection, such as respiratory tract, skin, ear, eye infections, and sexually transmitted diseases. The ongoing severe acute respiratory syndrome (SARS) mediated by Corona Virus 2 (CoVid19) is a global health concern and various countries witnessed the loss of precious human life. In fall 2020, the absence of specific suitable medication or vaccine is still a major cause of concern to fight the pandemic while different countries have already started using their own medication and available resources to save the life of their citizens. At the present, in many countries around the world, we witnessed the use of the antibiotic azithromycin towards the medication of CoVid19; even its effect on anti CoVid19 is still controversial. This mini review aims to address whether azithromycin can affect molecular pathway involved in inflammatory immunity upon viral infection, to find out the rationale behind the use of azithromycin in the treatment of CoVid19. Overall, the data show that the mechanism of action of azithromycin in viral infection may be dependent on a global amplification of the interferon-dependent pathways mediating antiviral responses, leading to a reduction of viral replication, together with a strong impairment of the inflammatory pathways, relying on MAPK cascade inactivation.