Coronaviruses are a family of RNA viruses that cause acute and chronic diseases of the upper and lower respiratory tract in humans and other animals. SARS-CoV-2 is a recently emerged coronavirus that has led to a global pandemic causing a severe respiratory disease known as COVID-19 with significant morbidity and mortality worldwide. The development of antiviral therapeutics are urgently needed while vaccine programs roll out worldwide. Here we describe a diamidobenzimidazole compound, diABZI-4, that activates STING and is highly effective in limiting SARS-CoV-2 replication in cells and animals. diABZI-4 inhibited SARS-CoV-2 replication in lung epithelial cells. Administration of diABZI-4 intranasally before or even after virus infection conferred complete protection from severe respiratory disease in K18-ACE2-transgenic mice infected with SARS-CoV-2. Intranasal delivery of diABZI-4 induced a rapid short-lived activation of STING, leading to transient proinflammatory cytokine production and lymphocyte activation in the lung associated with inhibition of viral replication. Our study supports the use of diABZI-4 as a host-directed therapy which mobilizes antiviral defenses for the treatment and prevention of COVID-19. Pharmacological activation of STING protects against SARS-CoV-2 infection.
【초록키워드】 COVID-19, Treatment, viruses, SARS-CoV-2, Vaccine, coronavirus, therapy, Antiviral, SARS-COV-2 infection, Human, lung, cytokine, chronic disease, global pandemic, lymphocyte, family, Viral, mice, animals, viral replication, RNA viruses, Respiratory disease, epithelial cells, morbidity and mortality, antiviral therapeutics, virus infection, respiratory, SARS-CoV-2 replication, STING, Lung epithelial cells, Lower respiratory tract, Support, Proinflammatory cytokine, Activation, severe respiratory disease, upper and lower respiratory tract, Defense, Complete, effective, Cell, prevention of COVID-19, PROTECT, intranasally, inhibited, RNA virus, activate, infected with SARS-CoV-2, short-lived, 【제목키워드】 PROTECT,