ABSTRACT Outbreaks of emerging viral pathogens like severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are a major medical challenge. There is a pressing need for antivirals that can be rapidly deployed to curb infection and dissemination. We determined the efficacy of interferon lambda-1 (IFN-λ) as a broad-spectrum antiviral agent to inhibit SARS-CoV-2 infection and reduce pathology in a mouse model of disease. IFN-λ significantly limited SARS-CoV-2 production in primary human bronchial epithelial cells in culture. Pretreatment of human lung cells with IFN-λ completely blocked infectious virus production, and treatment with IFN-λ at the time of infection inhibited virus production more than 10-fold. To interrogate the protective effects of IFN-λ in response to SARS-CoV-2 infection, transgenic mice expressing the human angiotensin-converting enzyme 2 (ACE-2) were tested. One dose of IFN-λ administered intranasally was found to reduce animal morbidity and mortality. Our study with SARS-CoV-2 also revealed a sex differential in disease outcome. Male mice had higher mortality, reflecting the more severe symptoms and mortality found in male patients infected with SARS-CoV-2. The results indicate that IFN-λ potentially can treat early stages of SARS-CoV-2 infection and decrease pathology, and this murine model can be used to investigate the sex differential documented in COVID-19.
【저자키워드】 COVID-19, SARS-CoV-2, Antiviral, interferon, Lung infection, murine model, 【초록키워드】 Treatment, pathology, Efficacy, coronavirus, Mortality, SARS-COV-2 infection, Infection, Sex, outcome, severe acute respiratory syndrome Coronavirus, ACE-2, Protective effects, Viral, Culture, mice, male, Patient, epithelial cells, Pathogens, morbidity and mortality, respiratory, dissemination, antiviral agent, mouse model, disease, early stage, protective effect, Human angiotensin-converting enzyme 2, Infectious virus, dose, angiotensin, acute respiratory syndrome, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, enzyme, human Angiotensin-converting enzyme, transgenic mice, early stages, treat, human lung cells, primary human bronchial epithelial cells, viral pathogens, viral pathogen, Interferon lambda, virus production, IFN-λ, Administered, decrease, tested, blocked, significantly, intranasally, inhibited, can be used, reduce, expressing, bronchial epithelial cell, severe symptom, human lung cell, infected with SARS-CoV-2, inhibit SARS-CoV-2, 【제목키워드】 protection, Model,