Lung Expression of Human Angiotensin-Converting Enzyme 2 Sensitizes the Mouse to SARS-CoV-2 Infection

Abstract

Ad5-empty+SARS-CoV-2 Ad5-hACE2+SARS-CoV-2 (high) Ad5-hACE2+SARS-CoV-2 (medium) Ad5-hACE2+SARS-CoV-2 (low) Figure E5

Therapeutically administered ribonucleoside analogue MK-4482/EIDD-2801 blocks SARS-CoV-2 transmission in ferrets

“…uninfected mice 14 . Spill-back of SARS-CoV-2 to farmed minks, subsequent large-scale mink-to-mink transmission and, in some cases, zoonotic transmission back to humans revealed efficient viral spread among members of the weasel genus without previous adaptation [6][7][8][9] .…”

Bispecific antibody neutralizes circulating SARS-CoV-2 variants, prevents escape and protects mice from disease

“…Weight was monitored daily for 8 days ( This approach enables rapid production of large cohorts of animals and has the advantage of being applicable to wild type and mutant mouse colonies, independently of age and gender. Moreover, since AAV vectors are only weakly immunogenic and cytotoxic, the system allows for prolonged expression of hACE2 [16][17][18][19] (Extended Data Fig.6). SARS-CoV-2 infection of ACE2 humanized 150 mice results in progressive weight loss, respiratory pathology and disease requiring culling on day 8 post infection (dpi, Fig.2a-c and Extended Data Fig.6).…”

Rapidly Deployable Mouse Models of SARS-CoV-2 Infection Add Flexibility to the COVID-19 Toolbox

“…In Ad5-hACE2 mice, SARS-CoV-2 replication is restricted to the respiratory tract, especially type 2 pneumocytes, and the infection is associated with mild to moderate interstitial and perivascular inflammation localized to areas of the lungs expressing hACE2 (4). The observation that the severity of SARS-CoV-2 infection may be tightly linked to the cellular and anatomical tropism provided by hACE2 distribution is supported by other SARS-CoV-2 mouse models.…”

“…The aim of these models is to replicate the human disease, or aspects thereof, as closely as possible, and while none currently utilized perfectly recapitulates either the biology or pathology of clinical infection, dependent on the question asked the use of several animal models should prove beneficial (as summarized in Figure 1). For example, the rapidly deployable Ad-or AAV-hACE2 models may be useful in screening anti-virals (4,13,14), while the K18-hACE2 mouse could be more useful in vaccine development. However, elucidating disease mechanisms is likely to require a more specific human ACE2 knock-in model or a mouse-adapted strain of SARS-CoV-2.…”