Spike protein recognition of mammalian ACE2 predicts the host range and an optimized ACE2 for SARS-CoV-2 infection

• Published in: Biochemical and biophysical research communications Vol. 526; no. 1; pp. 165 - 169
• Main Authors: Luan, Junwen, Lu, Yue, Jin, Xiaolu, Zhang, Leiliang
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21.05.2020
• Subjects: ACE2; Amino Acid Sequence; Angiotensin-Converting Enzyme 2; Animals; Betacoronavirus - physiology; Coronavirus Infections - metabolism; Coronavirus Infections - transmission; Coronavirus Infections - virology; COVID-19; COVID-19 infection; Cricetulus griseus; dogs; Host range; Humans; Mammals - classification; Mammals - metabolism; Models, Molecular; Pandemics; Peptidyl-Dipeptidase A - chemistry; Peptidyl-Dipeptidase A - metabolism; Pneumonia, Viral - metabolism; Pneumonia, Viral - transmission; Pneumonia, Viral - virology; public health; SARS-CoV-2; Sequence Alignment; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - chemistry; Spike Glycoprotein, Coronavirus - metabolism; Spike protein; Structure; Viral Tropism; Spike protein; E; JTT; M; N; COVID-19; ACE2; SARS-CoV-2; S; RBD; Host range; SARSr-CoV; Structure; RBM
• ISSN: 0006-291X; 1090-2104; 1090-2104
• DOI: 10.1016/j.bbrc.2020.03.047

SARS-CoV-2 causes the recent global COVID-19 public health emergency. ACE2 is the receptor for both SARS-CoV-2 and SARS-CoV. To predict the potential host range of SARS-CoV-2, we analyzed the key residues of ACE2 for recognizing S protein. We found that most of the selected mammals including pets (dog and cat), pangolin and Circetidae mammals remained the most of key residues for association with S protein from SARS-CoV and SARS-CoV-2. The interaction interface between cat/dog/pangolin/Chinese hamster ACE2 and SARS-CoV/SARS-CoV-2 S protein was simulated through homology modeling. We identified that N82 in ACE2 showed a closer contact with SARS-CoV-2 S protein than M82 in human ACE2. Our finding will provide important insights into the host range of SARS-CoV-2 and a new strategy to design an optimized ACE2 for SARS-CoV-2 infection. •Pets (dog and cat), pangolin and Circetidae remained the key residues for association with S from SARS-CoV and SARS-CoV-2.•The interface of the interaction between cat/dog/pangolin/Chinese hamster ACE2 and SARS-CoV/SARS-CoV-2 RBD was simulated.•N82 of ACE2 showed a closer contact with SARS-CoV-2 S than M82, suggesting an optimized ACE2 for SARS-CoV-2 infection.