부산대학교 도서관

Introduction and Hypothesis. Our group and others are using soluble ACE2 proteins to combat SARS-CoV-2. We have previously reported prevention of mortality, improvement of lung and kidney injury and reduced viral loads in SARS-CoV-2 infected mice that received a novel soluble ACE2 protein with extended duration of action and increased binding affinity for SARS-CoV-2, termed ACE2 618-DDC-ABD. In our previous study, this protein was administered both intranasally (IN) and intraperitoneally (IP). Here we tested the hypothesis that IN is more protective than IP administration.Methods: Human ACE2 618-DDC-ABD was tested in a BSL-3 facility in mice transgenic for human ACE2 (k18hACE2), infected with 3x10 PFU SARS-CoV-2. One hour before viral inoculation, the first protein dose was administered followed by 2 consecutive doses 24h and 48h post viral inoculation, either IN or IP (n=10 each). Weight, clinical score and mortality were monitored.Results: In the vehicle-receiving group (BSA in PBS), mortality was 100% on day 5. By contrast, in the IN-group, mortality was reduced markedly to only 10% on day 5 and 14. In the IP-group, by contrast, mortality was 60% at day 5 and 100% at day 14 (fig). In the IP-group, day 5 clinical scores [median (range)] were worse than in the IN-group [3.0 (2.0) and 1.0 (2.0), respectively, p=0.0032].Conclusions: This study confirms the dramatic improvement in survival in mice treated with an improved soluble ACE2 protein and demonstrates the superiority of IN over IP administration.