ACE2 partially dictates the host range and tropism of SARS-CoV-2

Abstract

COVID-19, which is caused by SARS-CoV-2, has been declared a global pandemic. Although effective strategies have been applied to treat the disease, much is still unknown about this novel virus. SARS-CoV-2 enters host cells through ACE2, which is a component of the angiotensin-regulating system. Binding of the SARS-CoV-2 S protein to ACE2 is a prerequisite for SARS-CoV-2 infection. Many studies have indicated a close relationship between ACE2 expression and SARS-CoV-2 infection. The structural basis of receptor recognition by SARS-CoV-2 has been analyzed in detail. The diversification of the ACE2 sequence due to ACE2 polymorphisms and alternative splicing has to a large extent affected the susceptibility of different species. Differential ACE2 expression makes specific populations more prone to be infected, and ACE2 also plays a role in the broad tropism of SARS-CoV-2 in human organs and tissues. In this review, we comprehensively summarize how the ACE2 expression profile affects the host range and tropism of SARS-CoV-2, which will provide mechanistic insights into the susceptibilities and outcomes of SARS-CoV-2 infection.

Keywords: ACE2; COVID-19; Host range; Host tropism; SARS-CoV-2.

Graphical abstract

Fig. 1

Susceptibility and outcoming of SARS-CoV-2 infection is dependent on ACE2 expression profile. Upper: SARS-CoV-2 host range could be predicted based on ACE2 orthologs. Animal species which possess ACE2 that has binding capacity to SARS-CoV-2 S (in wine red) are potential hosts of SARS-CoV-2. Animals of which the ACE2 is not suitable for SARS-CoV-2 S binding (in black) are resistant to this virus. Middle: Although humans are generally susceptible to this novel virus, the outcoming of infection is partially affected by different race, gender, age, underlying disease, and even living habits. Bottom: Clinical data showed that multiple organs other than lung could be injured by SARS-CoV-2. Researches about organ and cellular tropism of SARS-CoV-2 (marked in the Figure) are accumulating especially with the application of single-cell sequencing. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)