Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2
Copyright policy )Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2
The recent emergence of a novel coronavirus (SARS-CoV-2) in China has caused significant public health concerns. Recently, ACE2 was reported as an entry receptor for SARS-CoV-2. In this study, we present the crystal structure of the C-terminal domain of SARS-CoV-2 (SARS-CoV-2-CTD) spike (S) protein in complex with human ACE2 (hACE2), which reveals a hACE2-binding mode similar overall to that observed for SARS-CoV. However, atomic details at the binding interface demonstrate that key residue substitutions in SARS-CoV-2-CTD slightly strengthen the interaction and lead to higher affinity for receptor binding than SARS-RBD. Additionally, a panel of murine monoclonal antibodies (mAbs) and polyclonal antibodies (pAbs) against SARS-CoV-S1/receptor-binding domain (RBD) were unable to interact with the SARS-CoV-2 S protein, indicating notable differences in antigenicity between SARS-CoV and SARS-CoV-2. These findings shed light on the viral pathogenesis and provide important structural information regarding development of therapeutic countermeasures against the emerging virus.
- Chinese Academy of Sciences China (People's Republic of)
- University of Science and Technology of China China (People's Republic of)
- Shanghai Advanced Research Institute China (People's Republic of)
- Shenzhen Third People’s Hospital China (People's Republic of)
- University of Chinese Academy of Sciences China (People's Republic of)
Models, Molecular, SARS-CoV-2, Peptidyl-Dipeptidase A, Virus Internalization, General Biochemistry, Genetics and Molecular Biology, Article, Betacoronavirus, Epitopes, Protein Domains, Severe acute respiratory syndrome-related coronavirus, Spike Glycoprotein, Coronavirus, Humans, Amino Acid Sequence, Angiotensin-Converting Enzyme 2, Sequence Alignment, Phylogeny
Models, Molecular, SARS-CoV-2, Peptidyl-Dipeptidase A, Virus Internalization, General Biochemistry, Genetics and Molecular Biology, Article, Betacoronavirus, Epitopes, Protein Domains, Severe acute respiratory syndrome-related coronavirus, Spike Glycoprotein, Coronavirus, Humans, Amino Acid Sequence, Angiotensin-Converting Enzyme 2, Sequence Alignment, Phylogeny
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