A stem-loop RNA (SLR) RIG-I agonist is effective in preventing and treating acute SARS-CoV-2 infection in mice. A single injection of SLR can clear chronic SARS-CoV-2 in immunocompromised mice. SLR is effective against the ancestral virus as well as variants of concern. As SARS-CoV-2 continues to cause morbidity and mortality around the world, there is an urgent need for the development of effective medical countermeasures. Here, we assessed the antiviral capacity of a minimal RIG-I agonist, stem-loop RNA 14 (SLR14), in viral control, disease prevention, post-infection therapy, and cross-variant protection in mouse models of SARS-CoV-2 infection. A single dose of SLR14 prevented viral infection in the lower respiratory tract and development of severe disease in a type I interferon (IFN-I)–dependent manner. SLR14 demonstrated remarkable prophylactic protective capacity against lethal SARS-CoV-2 infection and retained considerable efficacy as a therapeutic agent. In immunodeficient mice carrying chronic SARS-CoV-2 infection, SLR14 elicited near-sterilizing innate immunity in the absence of the adaptive immune system. In the context of infection with variants of concern (VOCs), SLR14 conferred broad protection against emerging VOCs. These findings demonstrate the therapeutic potential of SLR14 as a host-directed, broad-spectrum antiviral for early post-exposure treatment and treatment of chronically infected immunosuppressed patients. Graphical Abstract
【초록키워드】 Treatment, SARS-CoV-2, viral infection, Efficacy, therapy, Antiviral, Innate immunity, SARS-COV-2 infection, Infection, variants of concern, Prophylactic, virus, variants, type I interferon, RNA, Viral, mice, morbidity, therapeutic, VOCs, Immunocompromised, RIG-I, therapeutic agent, morbidity and mortality, respiratory, Mouse models, mouse model, disease, immunosuppressed patients, single dose, Protective, severe disease, Lower respiratory tract, Post-infection, Medical countermeasures, therapeutic potential, injection, acute SARS-CoV-2 infection, adaptive immune system, viral control, effective, absence, in viral, demonstrated, prevented, elicited, retained, 【제목키워드】 RNA, RIG-I, PROTECT,