key: cord-0920319-blgzze4f
authors: Jiang, Shibo; Lu, Lu; Du, Lanying; Debnath, Asim K.
title: A predicted receptor-binding and critical neutralizing domain in S protein of the novel human coronavirus HCoV-EMC
date: 2012-12-22
journal: J Infect
DOI: 10.1016/j.jinf.2012.12.003
sha: fe01116d5d2c38ae8b9c780cd0b385e485fee866
doc_id: 920319
cord_uid: blgzze4f

nan

A predicted receptor-binding and critical neutralizing domain in S protein of the novel human coronavirus HCoV-EMC Dear Editor, Most recently, Yuen and colleagues have prospected, in this journal, that the discovery of the novel human betacoronavirus 2c EMC/2012 (HCoV-EMC) may be the beginning of another SARS-like pandemic and the research preparedness against this potential pandemic is an important precautionary strategy. 1 The rapid identification of HCoV-EMC that caused a SARS-like disease in Saudi Arabia 2 is attributed to the success in discovery of the SARS coronavirus (SARS-CoV). 3 Therefore, the knowledge gained from the research on SARS-CoV and the structures of its spike (S) protein may provide a useful template for identifying receptor for HCoV-EMC and developing vaccines against HCoV-EMC. 4 SARS-CoV S protein consists of S1 and S2 subunits (Fig. 1a) . The S1 subunit contains the receptor-binding domain (RBD, residues 318e510) responsible for its binding to the angiotensin-converting enzyme 2 (ACE2) receptor. 5 We previously demonstrated that the RBD is also a critical neutralizing domain (CND), which could induce highly potent neutralizing antibody responses in the immunized animals and protect against SARS-CoV challenge. 6, 7 Therefore, the immunogen containing this CND is expected to be effective SARS vaccine candidates. 8 Sequence alignment of the RBD/CND in SARS-CoV S with that of the corresponding region (residues 377e662) in HCoV-EMC S protein revealed that both fragments have low homology (14% identity and 38% similarity). However, the core domain consisting of b-sheets and ahelices in both fragments have higher homology (23% identity and 61% similarity). Strikingly, six cysteines are located at the same sites in both fragments (Fig. 1b) , suggesting that they share conserved conformational structures.

Based on the X-ray crystal structure of the RBD/CND domain in the SARS-CoV S protein (PDB id: 2DD8), 9 the structure of the corresponding region in the HCoV-EMC S protein was predicted using the Swiss-Model Workplace homology modeling server. 10 The results indicate that like the RBD/CND domain in the SARS-CoV S protein, 9, 11 the fragment of residues 377e662 in HCoV-EMC S protein also contains a core domain consisting of 5 b-sheets (b1eb4, b7) and 3 a-helices (aAeaC) and a long extended loop containing 2 anti-parallel b-sheets (b5eb6) (Fig. 1c) . It has been demonstrated that the core in the RBD/CND domain of the SARS-CoV S protein is responsible for maintaining the overall conformation of the protein, while the extended loop is responsible for its binding with the receptor ACE2 or a neutralizing antibody. 9, 11 These findings suggest that the region (residues 377e662) in HCoV-EMC S protein may also serve as a RBD/CND and can be used as a probe to identify HCoV-EMC's receptor and as an immunogen to design vaccines to prevent HCoV-EMC infection. 9 with the corresponding region (residues 377e662) in the HCoV-EMC S protein. The secondary structure assignments are listed above the primary sequence with b-sheets highlighted as arrows and a-helices highlighted by cylinders, respectively. 9 The conserved cysteines are highlighted with red circles. (c) Crystal structures of the RBD/CND in SARS-CoV S protein S1 subunit 9 (1) and predicted structure of RBD/CND in HCoV-EMC S protein S1 subunit (2) . A core consists of a five-stranded anti-parallel b-sheet (b1eb4, b7) connecting with three short a-helices (aAeaC), and an extended loop contains two-stranded b-sheet (b5, b6). N* and C* stand for the N-and C-termini of RBD/ CND, respectively.

No reported conflicts.

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Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia

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Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus

Receptor-binding domain of SARS-CoV spike protein induces highly potent neutralizing antibodies: implication for developing subunit vaccine

Identification and characterization of novel neutralizing epitopes in the receptorbinding domain of SARS-CoV spike protein: revealing the critical antigenic determinants in inactivated SARS-CoV vaccine

The spike protein of SARS-CoV: a target for vaccine and therapeutic development

Structure of severe acute respiratory syndrome coronavirus receptor-binding domain complexed with neutralizing antibody

The SWISS-MODEL workspace: a web-based environment for protein structure homology modelling

Structure of SARS coronavirus spike receptor-binding domain complexed with receptor

SJ was supported by funding from 973 Programme of China (#2012CB519001). LL was supported by "Chen Guang" Project of SMEC and SEDF (11CG03).