Antiviral Nanobiologic Therapy Remodulates Innate Immune Responses to Highly Pathogenic Coronavirus

Highly pathogenic coronavirus (CoV) infection induces a defective innate antiviral immune response coupled with the dysregulated release of proinflammatory cytokines and finally results in acute respiratory distress syndrome (ARDS). A timely and appropriate triggering of innate antiviral response is crucial to inhibit viral replication and prevent ARDS. However, current medical countermeasures can rarely meet this urgent demand. Here, an antiviral nanobiologic named CoVR-MV is developed, which is polymerized of CoVs receptors based on a biomimetic membrane vesicle system. The designed CoVR-MV interferes with the viral infection by absorbing the viruses with maximized viral spike target interface, and mediates the clearance of the virus through its inherent interaction with macrophages. Furthermore, CoVR-MV coupled with the virus promotes a swift production and signaling of endogenous type I interferon via deregulating 7-dehydrocholesterol reductase (DHCR7) inhibition of interferon regulatory factor 3 (IRF3) activation in macrophages. These sequential processes re-modulate the innate immune responses to the virus, trigger spontaneous innate antiviral defenses, and rescue infected Syrian hamsters from ARDS caused by SARS-CoV-2 and all tested variants.

Automated summary

Highly pathogenic coronavirus infection leads to defective innate immune response and excessive release of proinflammatory cytokines, resulting in acute respiratory distress syndrome (ARDS). A new antiviral nanobiologic, CoVR-MV, has been developed to interfere with viral infection and promote innate antiviral defenses. CoVR-MV absorbs viruses through its viral spike target interface, interacts with macrophages to clear the virus, and stimulates the production of endogenous type I interferon. These processes modulate the innate immune responses, activate antiviral defenses, and rescue Syrian hamsters from ARDS caused by SARS-CoV-2 and its variants.