Baicalin Induces a Potent Innate Immune Response to Inhibit Respiratory Syncytial Virus Replication via Regulating Viral Non-Structural 1 and Matrix RNA

Abstract

Respiratory syncytial virus (RSV) infection is the most frequent cause of hospitalization in pediatric patients. Current systemic treatment and vaccines are not curative and re-infection is often associated with a more drastic incidence of the disease. Baicalin is a flavonoid isolated from Scutellaria baicalensis with potent anti-viral characteristics, namely against RSV. However, its precise mechanism of action remains unclear. Here, using in vitro methods and an in vivo murine model of RSV infection, we showed that baicalin inhibits RSV replication induces translational upregulation of type I interferons (IFNs), IFN-α and IFN-β, and reverses epithelial thickening in lung tissues. Moreover, baicalin inhibits transcription of the RSV non-structural proteins NS1 and NS2. Molecular docking and surface plasmon resonance-based affinity analysis showed that baicalin also binds to the α3 helix of the NS1 protein with an affinity constant of 1.119 × 10−5 M. Polysome profiling showed that baicalin inhibits translation of the RSV matrix protein (M) RNA. Baicalin mediates increased release of the ribosomal protein L13a from the large ribosomal subunit, where the extra ribosomal subunit L13a inhibits M RNA translation. These results comprehensively establish the multiple mechanisms by which baicalin induces a potent innate immune response against RSV infection.

Baicalin Protects Broilers against Avian Coronavirus Infection via Regulating Respiratory Tract Microbiota and Amino Acid Metabolism

“…In the current study, we found that IBV RNA copies were decreased at 36 hpi in IBV-infected cells after being treated with Bai. Our results were consistent with previous studies, which confirmed that Bai exerted anti-IBV effects [21,22]. Despite achieving satisfactory results in vitro, some drugs showed poor efficacy in animal experimentation.…”

Baicalin inhibits influenza A (H1N1)‐induced pyroptosis of lung alveolar epithelial cells via caspase‐3/GSDME pathway

“…Baicalin has a broad‐spectrum antiviral effect through multiple mechanisms, such as targeting virus internalization, limiting autophagosome formation, and inducing innate immune response, 20–22 which have been repeatedly reported. To determine the effect of baicalin against H1N1 in vivo, mice were treated with baicalin 2 days before infection till 10 days after, with body weight and mortality being monitored for consecutive 17 days postviral challenge (Figure 1A).…”

Flavonoids Biosynthesis in Plants as a Defense Mechanism: Role and Function Concerning Pharmacodynamics and Pharmacokinetic Properties

“…Baicalin may prevent CHIKV infection because of its high binding affinity (À9.8 kcal/mol) for the CHIKV nsP3 protein. Lutein prevents HIV-1 reactivation by blocking clade Band C-Tat-driven LTR transactivation [202][203][204][205] . By reducing the binding of the transcription factor Sp1, luteolin prevented the reactivation of the Epstein-Barr virus (EBV).…”