Literature detail

Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus.

Yushun Wan1 Jian Shang1 Rachel Graham2 Ralph S Baric2 Fang Li3
Affiliations 3 institutions
  1. Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA.
  2. Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA.
  3. Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA [email protected].
PMID 31996437 2020 J Virol eng epublish
PubMed DOI Browse context

Article

Publication summary

Recently, a novel coronavirus (2019-nCoV) has emerged from Wuhan, China, causing symptoms in humans similar to those caused by severe acute respiratory syndrome coronavirus (SARS-CoV). Since the SARS-CoV outbreak in 2002, extensive structural analyses have revealed key atomic-level interactions between the SARS-CoV spike protein receptor-binding domain (RBD) and its host receptor angiotensin-converting enzyme 2 (ACE2), which regulate both the cross-species and human-to-human transmissions of SARS-CoV. Here, we analyzed the potential receptor usage by 2019-nCoV, based on the rich knowledge about SARS-CoV and the newly released sequence of 2019-nCoV. First, the sequence of 2019-nCoV RBD, including its receptor-binding motif (RBM) that directly contacts ACE2, is similar to that of SARS-CoV, strongly suggesting that 2019-nCoV uses ACE2 as its receptor. Second, several critical residues in 2019-nCoV RBM (particularly Gln493) provide favorable interactions with human ACE2, consistent with 2019-nCoV's capacity for human cell infection. Third, several other critical residues in 2019-nCoV RBM (particularly Asn501) are compatible with, but not ideal for, binding human ACE2, suggesting that 2019-nCoV has acquired some capacity for human-to-human transmission. Last, while phylogenetic analysis indicates a bat origin of 2019-nCoV, 2019-nCoV also potentially recognizes ACE2 from a diversity of animal species (except mice and rats), implicating these animal species as possible intermediate hosts or animal models for 2019-nCoV infections. These analyses provide insights into the receptor usage, cell entry, host cell infectivity and animal origin of 2019-nCoV and may help epidemic surveillance and preventive measures against 2019-nCoV.<b>IMPORTANCE</b> The recent emergence of Wuhan coronavirus (2019-nCoV) puts the world on alert. 2019-nCoV is reminiscent of the SARS-CoV outbreak in 2002 to 2003. Our decade-long structural studies on the receptor recognition by SARS-CoV have identified key interactions between SARS-CoV spike protein and its host receptor angiotensin-converting enzyme 2 (ACE2), which regulate both the cross-species and human-to-human transmissions of SARS-CoV. One of the goals of SARS-CoV research was to build an atomic-level iterative framework of virus-receptor interactions to facilitate epidemic surveillance, predict species-specific receptor usage, and identify potential animal hosts and animal models of viruses. Based on the sequence of 2019-nCoV spike protein, we apply this predictive framework to provide novel insights into the receptor usage and likely host range of 2019-nCoV. This study provides a robust test of this reiterative framework, providing the basic, translational, and public health research communities with predictive insights that may help study and battle this novel 2019-nCoV.

2019-nCoV angiotensin-converting enzyme 2 animal reservoir cross-species transmission human-to-human transmission SARS coronavirus Amino Acid Sequence Angiotensin-Converting Enzyme 2 Animals Betacoronavirus China Chiroptera Coronavirus Infections COVID-19 Host Specificity Humans Models, Molecular Peptidyl-Dipeptidase A

Structured evidence records

Evidence records

4 total
2 records
Extraction confidence 1.00
Key finding

2019-nCoV (SARS-CoV-2) likely uses angiotensin-converting enzyme 2 (ACE2) as its receptor for host cell entry, supported by similarity in its receptor-binding motif to SARS-CoV.

Virus
Location
Not specified
Supporting text

The sequence of 2019-nCoV RBD, including its receptor-binding motif (RBM) that directly contacts ACE2, is similar to that of SARS-CoV, strongly suggesting that 2019-nCoV uses ACE2 as its receptor.

Method
sequence analysis
Receptors
ACE2
Extraction confidence 1.00
Key finding

2019-nCoV can potentially use ACE2 receptors from multiple animal species except mice and rats, indicating broad receptor compatibility that may facilitate cross-species transmission.

Virus
Host
Location
Not specified
Supporting text

2019-nCoV also potentially recognizes ACE2 from a diversity of animal species (except mice and rats), implicating these animal species as possible intermediate hosts or animal models for 2019-nCoV infections.

Method
sequence comparison; phylogenetic analysis
Receptors
ACE2
1 records
Extraction confidence 0.80
Key finding

Sequence comparison and phylogenetic analysis show that 2019-nCoV is closely related to SARS-CoV and likely originated from bats.

Virus
Host
Location
Not specified
Supporting text

The sequence of 2019-nCoV RBD, including its receptor-binding motif, is similar to that of SARS-CoV, and phylogenetic analysis indicates a bat origin of 2019-nCoV.

Genes or proteins
spike; receptor-binding domain
Analysis methods
sequence alignment; phylogenetic analysis
1 records
Extraction confidence 0.90
Key finding

Residues Gln493 and Asn501 in the SARS-CoV-2 spike receptor-binding motif enhance interaction with human ACE2, supporting molecular adaptation for human infection.

Virus
Host
Not specified
Location
Not specified
Supporting text

Several critical residues in 2019-nCoV receptor-binding motif (particularly Gln493 and Asn501) provide favorable interactions with human ACE2, consistent with its capacity for human cell infection and partial adaptation for human-to-human transmission.

Genes or proteins
spike; receptor-binding domain; receptor-binding motif
Receptors
ACE2
Mutations
Gln493; Asn501
Mechanism types
receptor_binding; cell_entry