The COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the defining global health emergency of this century. GC-376 is a M pro inhibitor with antiviral activity against SARS-CoV-2 in vitro. Using the K18-hACE2 mouse model, the in vivo antiviral efficacy of GC-376 against SARS-CoV-2 was evaluated. GC-376 treatment was not toxic in K18-hACE2 mice. Overall outcome of clinical symptoms and survival upon SARS-CoV-2 challenge were not improved in mice treated with GC-376 compared to controls. The treatment with GC-376 slightly improved survival from 0 to 20% in mice challenged with a high virus dose at 10 5 TCID50/mouse. Most notably, GC-376 treatment led to milder tissue lesions, reduced viral loads, fewer presence of viral antigen, and reduced inflammation in comparison to vehicle-treated controls in mice challenged with a low virus dose at 10 3 TCID50/mouse. This was particularly the case in the brain where a 5-log reduction in viral titers was observed in GC-376 treated mice compared to vehicle controls. This study supports the notion that GC-376 represents a promising lead candidate for further development to treat SARS-CoV-2 infection and that the K18-hACE2 mouse model is suitable to study antiviral therapies against SARS-CoV-2.
【저자키워드】 SARS-CoV-2, Microbiology, Virology, 【초록키워드】 Treatment, Inflammation, antiviral therapy, Clinical symptoms, SARS-COV-2 infection, COVID-19 pandemic, severe acute respiratory syndrome coronavirus-2, in vitro, antiviral activity, outcome, severe acute respiratory syndrome Coronavirus, virus, Brain, hACE2, Severe acute respiratory syndrome, survival, Viral, mice, Control, antiviral efficacy, K18-hACE2 mice, respiratory, in vivo, inhibitor, K18-hACE2, dose, lead, antiviral therapies, Support, health emergency, Viral antigen, not improved, acute respiratory syndrome coronavirus, clinical symptom, M pro, reduced viral loads, viral loads, treat, viral titers, toxic, MOST, viral titer, controls, tissue lesions, caused, evaluated, reduced, treated, reduction in, 【제목키워드】 SARS-CoV-2 virus infection, Transgenic mouse, K18,