The Hybrid of Cu─TCPP@Mn3O4 for Inflammation Relief by ROS Scavenging and O2 Production: An Efficient Strategy for Antiviral Therapy

Abstract Seasonal influenza still greatly threatens public health worldwide, leading to significant morbidity and mortality. Antiviral medications for influenza treatment are limited and accompanied by increased drug resistance. In severe influenza virus infection, hyperinflammation and hypoxia may be the significant threats associated with mortality, so the development of effective therapeutic methods to alleviate excessive inflammation while reducing viral damage is highly pursued. Here, a multifunctional MOF‐based nanohybrid of Cu─TCPP@Mn 3 O 4 as a novel drug against influenza A virus infection (MOF = metal−organic framework; TCPP = tetrakis (4‐carboxyphenyl) porphyrin) is designed. Cu─TCPP@Mn 3 O 4 exhibits potent inhibitory capability against influenza A virus infection in vitro and in vivo. The mechanism study reveals that Cu─TCPP@Mn 3 O 4 inhibits the virus entry by binding to the HA2 subunit of influenza A virus hemagglutinin. In addition, the nanoparticles of Mn 3 O 4 in Cu─TCPP@Mn 3 O 4 can scavenge intracellular ROS with O 2 generation to downregulate inflammatory factors and effectively inhibit cytokines production. By reconstructing the antioxidant microenvironment, Cu─TCPP@Mn 3 O 4 features as a promising nanomedicine with anti‐inflammatory and anti‐viral synergistic effects.