Expression pattern and function of SARS-CoV-2 receptor ACE2

Abstract

Since the outbreak at the end of 2019, SARS-CoV-2 has been spreading around the world for more than one year. Scientists have been intensely conducting research on this newly emerged coronavirus and the disease caused by it. Angiotensin-converting enzyme 2 (ACE2), as a receptor mediating the cellular entry of SARS-CoV-2, has become a hot spot for researchers. Here, we summarized the recent progresses on the function, expression and distribution characteristics of ACE2 in human body and among populations. We further discussed the interaction mechanism of ACE2 and SARS-CoV-2 S protein, focusing on key residues that effect interaction and binding ability of SARS-CoV-2 variants. This will facilitate researchers to better understand SARS-CoV-2 infection and transmission route, adaptation mechanism, and designing treatment strategies.

Keywords: ACE2; Expression pattern; Interaction; SARS-CoV-2.

Fig. 1

Dotplot deciphering tissue expression pattern of ACE2 and TMPRSS2. RNA HPA tissue gene data, TPM (Transcripts Per Kilobase of exon model per Million mapped reads) represent transcript expression levels summarized per gene in 36 tissues based on RNA-Seq, https://www.proteinatlas.org/about/download.

Fig. 2

Major cell types from different organs/tissues that expressing ACE2 and TMPRSS2. Cell types expressing ACE2 were marked in purple. Cell types expressing TMPRSS2 were marked in green. This figure is created with Biorender.com.

Fig. 3

Segments where hACE2 interacts with SARS-COV-2 S protein, and sequence alignment of these segments in other putative host animals. The amino acids marked in red indicate they have H-bond or salt bridge interactions with hACE2. The listed animals are Homo sapiens (human), Mus musculus (mouse), Rattus norveicus (rat), Rhinologhus macrotis (bat), Macaca mulatta (monkey), Pan trolodytes (orangutan), Mustela putorius furo (ferret), Felis catus (cat), Canius lupus familiaris (dog) and Bos taurus (cow).