Broad‐spectrum antiviral effect of MoringaA‐loaded exosomes against IAV by mediating the GCN5‐TFEB‐autolysosome pathway

Abstract Influenza virus‐induced viral pneumonia is a major threat to human health, and specific therapeutic agents for viral pneumonia are still lacking. MoringaA (MA) is an anti‐influenza virus active compound isolated from Moringa seeds, which can inhibit influenza virus by activating the TFEB‐autophagic lysosomal pathway in host cells. In this study, we obtained exosomes from M2‐type macrophages and encapsulated and delivered MA (MA‐Exos), and we investigated the efficacy of MA‐Exos in antiviral and viral pneumonia in vivo and in vitro, respectively. In addition, we provided insights into the mechanism by which MA‐Exos regulates TFEB‐lysosomal autophagy by RNA sequencing. The MA‐Exos showed broad‐spectrum inhibition of IAV, and significant promotion of the autophagic lysosomal pathway. Meanwhile, we found that GCN5 gene and protein were significantly down‐regulated in IAV‐infected cells after MA‐Exos intervention, indicating its blocking the acetylation of TFEB by GCN5. In addition, MA‐Exos also significantly promoted autophagy in lung tissue cells of mice with viral pneumonia. MA‐Exos can inhibit and clear influenza virus by mediating the TFEB‐autophagy lysosomal pathway by a mechanism related to the down‐regulation of histone acetyltransferase GCN5. Our study provides a strategy for targeting MA‐Exos for the treatment of viral pneumonia from both antiviral and virus‐induced inflammation inhibition pathways.