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Compound class: Synthetic organic
Comment: Structurally SLR14 is a synthetic looped 14-bp RNA duplex that is 5'-tri-phosphorylated (with sequence 5′-pppGGAUCGAUCGAUCGUUCGCGAUCGAUCGAUCC-3′) , whose duplex terminus binds to the RIG-I-like receptor and cytosolic RNA sensor RIG-1. Functionally, SLR14 mimics RIG-1 ligands from RNA viruses, and it selectively stimulates a type I interferon antiviral response. In vivo work using the K18-hACE2 mouse model demonstrates the therapeutic potential of RIG-1 agonism to reduce/prevent SARS-CoV-2 infection and combat viral disease pathology. In the mouse model, SLR14 protects from SARS-CoV-2 infection and COVID-19 pathologies. It prevents infection by all SARS-CoV-2 variants tested, B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), B.1.617.2 (Delta) and B.1.526 (Iota), and can resolve persistent SARS-CoV-2 infection in immunodeficient mice.