Generation of a Broadly Useful Model for COVID-19 Pathogenesis, Vaccination, and Treatment | Zendy

Jing Sun | Zendy; Zhen Zhuang | Zendy; Jian Zheng | Zendy; Kun Li | Zendy; Lok-Yin Roy Wong | Zendy; Donglan Liu | Zendy; Jicheng Huang | Zendy; Jiangping He | Zendy; Airu Zhu | Zendy; Jingxian Zhao | Zendy; Xiaobo Li | Zendy; Xi Yin | Zendy; Rongchang Chen | Zendy; Abeer N. Alshukairi | Zendy; Chen Zhao | Zendy; Zhaoyong Zhang | Zendy; Chunke Chen | Zendy; Xiaofang Huang | Zendy; Fang Li | Zendy; Xiaomin Lai | Zendy; Dingbin Chen | Zendy; Liyan Wen | Zendy; Jianfen Zhuo | Zendy; Yanjun Zhang | Zendy; Yanqun Wang | Zendy; Shuxiang Huang | Zendy; Jun Dai | Zendy; Yongxia Shi | Zendy; Kui Zheng | Zendy; Mariah Leidinger | Zendy; Jiekai Chen | Zendy; Yimin Li | Zendy; Nanshan Zhong | Zendy; David K. Meyerholz | Zendy; Paul B. McCray | Zendy; Stanley Perlman | Zendy; Jincun Zhao | Zendy

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Generation of a Broadly Useful Model for COVID-19 Pathogenesis, Vaccination, and Treatment

Author(s) -

Jing Sun,

Zhen Zhuang,

Jian Zheng,

Kun Li,

Lok-Yin Roy Wong,

Donglan Liu,

Jicheng Huang,

Jiangping He,

Airu Zhu,

Jingxian Zhao,

Xiaobo Li,

Xi Yin,

Rongchang Chen,

Abeer N. Alshukairi,

Chen Zhao,

Zhaoyong Zhang,

Chunke Chen,

Xiaofang Huang,

Fang Li,

Xiaomin Lai,

Dingbin Chen,

Liyan Wen,

Jianfen Zhuo,

Yanjun Zhang,

Yanqun Wang,

Shuxiang Huang,

Jun Dai,

Yongxia Shi,

Kui Zheng,

Mariah Leidinger,

Jiekai Chen,

Yimin Li,

Nanshan Zhong,

David K. Meyerholz,

Paul B. McCray,

Stanley Perlman,

Jincun Zhao

Publication year - 2020

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2020.06.010

Subject(s) - biology , covid-19 , vaccination , virology , pathogenesis , pandemic , computational biology , immunology , outbreak , disease , infectious disease (medical specialty) , medicine , pathology

COVID-19, caused by SARS-CoV-2, is a virulent pneumonia, with >4,000,000 confirmed cases worldwide and >290,000 deaths as of May 15, 2020. It is critical that vaccines and therapeutics be developed very rapidly. Mice, the ideal animal for assessing such interventions, are resistant to SARS-CoV-2. Here, we overcome this difficulty by exogenous delivery of human ACE2 with a replication-deficient adenovirus (Ad5-hACE2). Ad5-hACE2-sensitized mice developed pneumonia characterized by weight loss, severe pulmonary pathology, and high-titer virus replication in lungs. Type I interferon, T cells, and, most importantly, signal transducer and activator of transcription 1 (STAT1) are critical for virus clearance and disease resolution in these mice. Ad5-hACE2-transduced mice enabled rapid assessments of a vaccine candidate, of human convalescent plasma, and of two antiviral therapies (poly I:C and remdesivir). In summary, we describe a murine model of broad and immediate utility to investigate COVID-19 pathogenesis and to evaluate new therapies and vaccines.

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