J Virol. 2020 Jan 29. pii: JVI.00127-20. doi: 10.1128/JVI.00127-20. [Epub ahead of print]
Receptor recognition by novel coronavirus from Wuhan: An analysis based on decade-long structural studies of SARS.
Abstract
Recently
a novel coronavirus (2019-nCoV) has emerged from Wuhan, China, causing
symptoms in humans similar to those caused by SARS coronavirus
(SARS-CoV). Since SARS-CoV outbreak in 2002, extensive structural
analyses have revealed key atomic-level interactions between 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.
Significance
The recent emergence of Wuhan coronavirus (2019-nCoV) puts the world on alert. 2019-nCoV is reminiscent of the SARS-CoV outbreak in 2002-2003. 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.
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.
Significance
The recent emergence of Wuhan coronavirus (2019-nCoV) puts the world on alert. 2019-nCoV is reminiscent of the SARS-CoV outbreak in 2002-2003. 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.
Copyright © 2020 American Society for Microbiology.
- PMID:
- 31996437
- DOI:
- 10.1128/JVI.00127-20
Inga kommentarer:
Skicka en kommentar