Carbonized Nanogels Derived from Quercetin as a Potential Antiviral and Anti-Inflammatory Agent Against Influenza A Virus

Abstract

Influenza 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 that target the M2 ion channel and the neuraminidase can 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 controlled carbonization of quercetin, which preserved its antioxidative properties while also acquiring enhanced properties, such as water solubility, viral binding, anti-inflammatory activity, and biocompatibility. Antiviral assays of co-treatment, pre-treatment, and post-treatment indicate that CNGs_Qur interact with the virion, revealing that the major antiviral mechanism resulting in the inhibition of the virus occurs by attachment on the cell surface. Compared with quercetin, the combined effects of viral inhibition, antioxidative activity, and anti-inflammatory activity impart the CNGs_Qur with superior therapeutic effects to treat H1N1 virus infection, as evidenced by a mouse model. These _Qur effectively prevent the spread of IAVs and suppress virus-induced inflammation while also exhibiting good in vivo biocompatibility. CNGs_Qur show much promise as a clinical therapeutic agent against infection by IVAs.

Keywords: Phytochemicals, Antioxidants, Inflammatory regulation, Antiviral carbon nanomaterials, Virus attachment