Elucidating the inhibitory role of miR-140-5p in SARS-CoV-2 infection.

The ongoing COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has necessitated an urgent need for understanding the molecular mechanisms underlying viral infection and host response. MicroRNAs (miRNAs) have emerged as key regulators in viral pathogenesis, mediating complex interactions between the virus and the host's cellular machinery. In this study, we identify miR-140-5p as a significant factor in the regulation of SARS-CoV-2 entry into host cells. Through comprehensive RNA sequencing analysis of peripheral blood mononuclear cells from COVID-19 patients, we observed significant alterations in the expression of miR-140-5p and its target genes during infection. Further bioinformatics analysis revealed that miR-140-5p targets are predominantly associated with endocytosis-related signaling pathways, suggesting a mechanism by which miR-140-5p may influence SARS-CoV-2 entry. Experimental validation using miR-140-5p mimics demonstrated a significant reduction in viral entry across multiple SARS-CoV-2 variants, confirming the inhibitory role of miR-140-5p on viral replication. These findings suggest that miR-140-5p could potentially be explored as a target for inhibiting viral entry, providing new insights into the role of host miRNAs in SARS-CoV-2 infection and the development of antiviral strategies.