High-Lethality Precision-Guided Nanomissile for Broad-Spectrum Virucidal and Anti-Inflammatory Therapy.

Viral infection, especially the past SARS-CoV-2 pandemic, has posed severe threat toward globalized healthcare, whereas vaccine and drug development can hardly keep up with the rate of virus mutation and resistance. In severe COVID-19 patients, the virus triggers a cytokine storm marked by excessive pro-inflammatory cytokine release, resulting in acute respiratory distress syndrome (ARDS). Therefore, a comprehensive strategy for viral neutralization and inflammation suppression is highly demanded. Herein, we designed a high-lethality precision-guided nanomissile for broad-spectrum virucidal and anti-inflammatory therapy. The nanomissile was a nanoscale molecularly imprinted polymer (nanoMIP) harboring hypervalent mannose-binding cavities and loaded with a magnetocaloric core and photothermal dye ICG. It demonstrated an ultrafast heating rate, increasing from 25.2 to 55.9 °C within 60 s under alternating magnetic field (AMF) and near-infrared (NIR) laser irradiation. In addition, the nanomissile exhibited a unique double-punch mechanism, being capable of targeting not only the conserved high-mannose glycans of SARS-CoV-2, HIV-1, LASV, and PDCoV with Kd values reaching 10-10 M but also heat-inactivating the virions right away. Beyond this, it also exhibited significant anti-inflammatory and immunomodulatory properties. In the mouse model, the nanomissile exerted outstanding therapeutic and prophylactic effects while inhibiting virus replication and protecting lung injury. Thus, this potently broad-spectrum virucidal strategy opens a new access to eradicating viral infectivity and inflammatory storm suspension.