The SARS-CoV-2 pandemic has underscored the need for rapidly usable prophylactic and antiviral treatments against emerging viruses. The targeted stimulation of antiviral innate immune receptors can trigger a broad antiviral response that also acts against new, unknown viruses. Here, we used the K18-hACE2 mouse model of COVID-19 to examine whether activation of the antiviral RNA receptor RIG-I protects mice from lethal SARS-CoV-2 infection and reduces disease severity. We found that prophylactic, systemic treatment of mice with the specific RIG-I ligand 3pRNA, but not type I interferon, 1–7 days before viral challenge, improved survival of mice by up to 50%. Survival was also improved with therapeutic 3pRNA treatment starting 1 day after viral challenge. This improved outcome was associated with lower viral load in oropharyngeal swabs and in the lungs and brains of 3pRNA-treated mice. Moreover, 3pRNA-treated mice exhibited reduced lung inflammation and developed a SARS-CoV-2-specific neutralizing antibody response. These results demonstrate that systemic RIG-I activation by therapeutic RNA oligonucleotide agonists is a promising strategy to convey effective, short-term antiviral protection against SARS-CoV-2 infection, and it has great potential as a broad-spectrum approach to constrain the spread of newly emerging viruses until virus-specific therapies and vaccines become available.
【저자키워드】 COVID-19, SARS-CoV-2, coronavirus, pandemic, Innate immunity, RIG-I, antiviral immunity, emerging viruses, K18-hACE2 mouse model, Type I IFN, MT: Oligonucleotides: Therapies and Applications, nucleic acid immunity, 【초록키워드】 Treatment, viruses, Vaccine, therapy, Antiviral, SARS-COV-2 infection, SARS-CoV-2 pandemic, disease severity, lung, Antiviral treatment, outcome, Prophylactic, type I interferon, Brain, RNA, Spread, survival, Viral load, mice, oropharyngeal swab, therapeutic, receptor, Neutralizing antibody response, K18-hACE2, innate immune, antiviral response, Ligand, Lung inflammation, viral challenge, Activation, agonist, approach, effective, PROTECT, virus, reduced, exhibited, reduce, 【제목키워드】 SARS-COV-2 infection, mice, innate antiviral immunity, PROTECT,