Azithromycin: Molecular and Clinical Insights into its Antiviral and Immunomodulatory Actions Against Global Health Threats

The significant impact of viral infections on public health has underscored the urgent need for effective antiviral treatments. Among macrolides, azithromycin has gained attention for its broad-spectrum antiviral activity against several well-known viruses, including SARS-CoV, Zika virus, Ebola virus, Enteroviruses (EVs), Rhinoviruses (RVs), and Influenza A virus. These viruses pose serious global health threats, necessitating the exploration of new therapeutic strategies. Notably, during the COVID-19 pandemic caused by SARS-CoV-2, azithromycin was extensively investigated due to its potential antiviral and immune-modulating effects. This review aims to provide a comprehensive analysis of the molecular mechanisms underlying azithromycin’s antiviral action, emphasizing its interference with viral replication, modulation of the host immune response, and effects on cellular pathways crucial for viral infections. Additionally, the review will examine the clinical applications of azithromycin in the treatment of viral infections, with a particular focus on COVID-19. Furthermore, we will discuss the structure-activity relationship of azithromycin, highlighting how its molecular framework contributes to its antiviral efficacy. By integrating mechanistic insights with clinical evidence, this review seeks to offer a well-rounded perspective on azithromycin as a potential antiviral agent.