tetano
Editor, Senior Moderator
Cell. 2020 Apr 7. pii: S0092-8674(20)30338-X. doi: 10.1016/j.cell.2020.03.045. [Epub ahead of print]
Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2.
Wang Q[SUP]1[/SUP], Zhang Y[SUP]2[/SUP], Wu L[SUP]3[/SUP], Niu S[SUP]4[/SUP], Song C[SUP]5[/SUP], Zhang Z[SUP]6[/SUP], Lu G[SUP]7[/SUP], Qiao C[SUP]8[/SUP], Hu Y[SUP]9[/SUP], Yuen KY[SUP]10[/SUP], Wang Q[SUP]11[/SUP], Zhou H[SUP]11[/SUP], Yan J[SUP]12[/SUP], Qi J[SUP]13[/SUP].
Author information
Abstract
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.
Copyright ? 2020 Elsevier Inc. All rights reserved.
KEYWORDS:
ACE2; CTD; SARS-CoV-2; crystal structure; immunogenicity; receptor; receptor binding domain
PMID:32275855PMCID:PMC7144619DOI:10.1016/j.cell.2020.03.045
Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2.
Wang Q[SUP]1[/SUP], Zhang Y[SUP]2[/SUP], Wu L[SUP]3[/SUP], Niu S[SUP]4[/SUP], Song C[SUP]5[/SUP], Zhang Z[SUP]6[/SUP], Lu G[SUP]7[/SUP], Qiao C[SUP]8[/SUP], Hu Y[SUP]9[/SUP], Yuen KY[SUP]10[/SUP], Wang Q[SUP]11[/SUP], Zhou H[SUP]11[/SUP], Yan J[SUP]12[/SUP], Qi J[SUP]13[/SUP].
Author information
Abstract
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.
Copyright ? 2020 Elsevier Inc. All rights reserved.
KEYWORDS:
ACE2; CTD; SARS-CoV-2; crystal structure; immunogenicity; receptor; receptor binding domain
PMID:32275855PMCID:PMC7144619DOI:10.1016/j.cell.2020.03.045