Since the pandemic of COVID-19 has intensely struck human society, small animal model for this infectious disease is in urgent need for basic and pharmaceutical research. Although several COVID-19 animal models have been identified, many of them show either minimal or inadequate pathophysiology after SARS-CoV-2 challenge. Here, we describe a new and versatile strategy to rapidly establish a mouse model for emerging infectious diseases in one month by multi-route, multi-serotype transduction with recombinant adeno-associated virus (AAV) vectors expressing viral receptor. In this study, the proposed approach enables profound and enduring systemic expression of SARS-CoV-2-receptor hACE2 in wild-type mice and renders them vulnerable to SARS-CoV-2 infection. Upon virus challenge, generated AAV/hACE2 mice showed pathophysiology closely mimicking the patients with severe COVID-19. The efficacy of a novel therapeutic antibody cocktail RBD-chAbs for COVID-19 was tested and confirmed by using this AAV/hACE2 mouse model, further demonstrating its successful application in drug development. Author summary Upon the emergence of new infectious disease, animal model becomes a pivotal tool for study of disease mechanism and development of therapeutics. In this study, we propose a versatile approach that allows rapid generation of mouse model for novel infectious disease once the receptor of the pathogen is identified. We demonstrated this approach by generating a mouse model for COVID-19 in a month’s time. These mice were capable of recapitulating severe COVID-19 in patients, and successfully applied in the development of a therapeutic antibody cocktail for the disease. This not only suggests the usefulness of this mouse model for the research on COVID-19, but also exhibit the utility of the proposed approach for establishing animal model for infectious disease.
【초록키워드】 COVID-19, SARS-CoV-2, Efficacy, Infectious diseases, severe COVID-19, Drug development, Therapeutics, SARS-COV-2 infection, animal model, Infectious disease, virus, hACE2, pathogen, antibody cocktail, pathophysiology, mice, vector, therapeutic, Research, receptor, utility, mouse model, disease, expression, patients, mechanism, adeno-associated virus, multi, wild-type, vectors, pandemic of COVID-19, approach, receptor hACE2, the patient, the disease, applied, demonstrated, expressing, mimicking, was tested, 【제목키워드】 Rapid,