A review of targeting microRNAs as potential therapeutic strategies against respiratory viruses: Current insights and future directions.

Respiratory viruses such as influenza viruses, respiratory syncytial virus (RSV), and coronaviruses continue to impose a global health burden due to their high transmissibility and limited antiviral options. MicroRNAs (miRNAs) have emerged as critical regulators of host pathogen interactions by modulating innate immunity, inflammatory signaling, and viral replication. This review focuses on respiratory RNA and DNA viruses that primarily infect the airways, including influenza viruses, RSV, human metapneumovirus, rhinoviruses, adenoviruses, and SARS-CoV-2. Several miRNAs, including miR-155 and miR-146a, are upregulated during infections with SARS-CoV-2, influenza, and RSV, where they fine-tune interferon and NF-κB signaling pathways. In contrast, downregulation of miR-21, miR-223, and let-7 family members has been linked to enhanced viral replication and dysregulated immune responses. Moreover, miR-122, miR-29a, and miR-124 have gained attention as potential therapeutic targets or prognostic biomarkers due to their roles in modulating viral load, cytokine production, and tissue injury. This review synthesizes current evidence on miRNA-mediated regulation of respiratory viruses, evaluates their promise as therapeutic candidates and diagnostic tools, and discusses delivery systems designed for targeted miRNA modulation. Despite promising advances, challenges remain in achieving tissue-specific delivery, avoiding immune off-target effects, and validating efficacy in clinical settings. Most of the available data are derived from in vitro or animal models and heterogeneous clinical cohorts, so conclusions about causality and therapeutic efficacy should be viewed as provisional and highlight significant translational gaps. Finally, we outline major challenges and future research directions needed to translate miRNA-targeted therapies into clinically viable antiviral strategies. Insights from these emerging studies position miRNA-targeted interventions as a potential new class of antiviral therapeutics and underscore the need for rigorous, translational research to realize their clinical utility.