Partial carbonization of quercetin boosts the antiviral activity against H1N1 influenza A virus

Inflenza A viruses (IAVs) are highly transmissible and pathogenic Orthomyxoviruses, which have led to worldwide outbreaks and seasonal pandemics of acute respiratory diseases, causing serious threats to public health. Currently used anti-influenza drugs may cause neurological side effects, and they are increasingly less effective against mutant strains. To help prevent the spread of IAVs, in this work, we have developed quercetin-derived carbonized nanogels (CNGs_Qur) that display potent viral inhibitory, antioxidative, and anti-inflammatory activities. The antiviral CNGs_Qur were synthesized by mild carbonization of quercetin (Qur), which successfully preserved their antioxidative and anti-inflammatory properties while also contributed enhanced properties, such as water solubility, viral binding, and biocompatibility. Antiviral assays of co-treatment, pre-treatment, and post-treatment indicate that CNGs_Qur interacts with the virion, revealing that the major antiviral mechanism resulting in the inhibition of the virus is by their attachment on the cell surface. Among them, the selectivity index (SI) of CNGs_Qur270 (>857.1) clearly indicated its great potential for clinical application in IAVs inhibition, which was much higher than that of pristine quercetin (63.7) and other clinical drugs (4-81). Compared with quercetin at the same dose, the combined effects of viral inhibition, antioxidative and anti-inflammatory activities impart the superior therapeutic effects of CNGs_Qur270 aerosol inhalation in the treatment of IAVs infection, as evidenced by a mouse model. These CNGs_Qur effectively prevent the spread of IAVs and suppress virus-induced inflammation while also exhibiting good in vivo biocompatibility. CNGs_Qur shows much promise as a clinical therapeutic agent against infection by IVAs.