Baicalin inhibits influenza virus A replication via activation of type I IFN signaling by reducing miR-146a

Influenza virus A (IVA) is one of the predominant causative agents of the seasonal flu and has become an important cause of morbidity worldwide. Great efforts have been paid to develop vaccines against IVA. However, due to antigenic drift in influenza virus A and rapid emergence of drug-resistant strains, current available vaccines or anti-IVA chemotherapeutics are consistently inefficient. Hence, various more broadly effective drugs have become important for the prevention and treatment of IVA. Of these drugs, baicalin, a flavonoid isolated from Radix Scutellaria, is a promising example. However, little is known in regards to its pharmacological mechanism. Here, it was demonstrated that baicalin inhibits the H1N1 and H3N2 viruses in A549 cells. Subsequently, it was found that miR-146a was markedly downregulated by treatment of baicalin. Additionally, further experiments revealed that miR-146a was able to promote the replication of H1N1 and H3N2 by targeting TNF receptor-associated factor 6 (TRAF6), a pivotal adaptor in the interferon (IFN) production signaling pathway, to downregulate type I IFN production, and enrichment of miR-146a eliminated the anti-IVA effects of baicalin on the H1N1 and H3N2 viruses. Additionally, in vivo experiments demonstrated that baicalin could protect mice during H1N1 infection. Taken together, our findings firstly illustrated the anti-IVA molecular mechanism of baicalin and provide new evidence for targeting miRNAs to prevent and treat viral infection, such as the H1N1 and H3N2 viruses.