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

By Yushun Wan, J. Shang, Rachel L. Graham, Ralph S. Baric, Fang Li. Journal of Virology, 2020

3,709 citations recorded by the source corpus.

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. ABSTRACT 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. IMPORTANCE 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.

Subfields: Infectious Diseases

View Paper: https://www.semanticscholar.org/paper/de51d9de79c41bdac948c4a2a88a7e372535451f

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In Infectious Diseases

Citations in the corpus

SARS-CoV-2 Vaccines: Status Report (2020, methodology): “Initial work showed that it can use angiotensin-converting enzyme 2 (ACE2) from bats, civet cats, swine, cats, ferrets, non-human primates (NHPs), and humans as a receptor (Letko et al., 2020;Wan et al., 2020; Zhou et al., 2020).”
SARS-CoV-2 Spike protein variant D614G increases infectivity and retains sensitivity to antibodies that target the receptor binding domain (2020, positive): “Structural and biochemical studies (Letko et al., 2020; Walls et al., 2020; Wrapp et al., 2020; Zhou et al., 2020b) have shown that SARS-CoV-2 bears a receptor binding domain with high affinity for ACE2 from humans, ferrets, cats, and other species that encode similar ACE2 (Wan et al., 2020).”
COVID-19 Vaccine: A comprehensive status report (2020, background): “MERS-CoV uses an entirely different receptor that is, Dipeptidyl Peptidase 4 (DPP4) (Wan et al., 2020) and the virus is distantly related to SARS-CoV-2 with around 50% similarity as per the sequence analysis of the two viruses (Prof Roujian et al., 2020).”
Structures of Human Antibodies Bound to SARS-CoV-2 Spike Reveal Common Epitopes and Recurrent Features of Antibodies (2020, neutral): “latively little is known about antibody recognition of SARSV-2 S compared with other coronavirus S proteins (Graham al., 2013; Gralinski and Baric, 2015; Wan et al., 2020).”
A Novel Bat Coronavirus Closely Related to SARS-CoV-2 Contains Natural Insertions at the S1/S2 Cleavage Site of the Spike Protein (2020, neutral): “In contrast, RaTG13 (Figure 2B), pangolin/MP789/2019 (Figure 2C), and pangolin/P5L/2017 (Figure 2D) did not have the deletions, and had similar conformations at their external domains, indicating that they may also use ACE2 as cell receptor, although with the exception of pangolin/MP789/2019 (see be”
Deep Mutational Scanning of SARS-CoV-2 Receptor Binding Domain Reveals Constraints on Folding and ACE2 Binding (2020, neutral): “An initially surprising feature of SARS-CoV-2 was that its RBD tightly binds ACE2 despite differing in sequence from SARS-CoV-1 at many residues that had been defined as important for ACE2 binding (Andersen et al., 2020; Wan et al., 2020).”
Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms (2020, background): “9 It is well-known that viral mutations occur during transmission and spreading.”
Genomic characterization of a novel SARS-CoV-2 (2020, background): “This area of ORF1ab is the most important factor among coronaviruses (Wan et al., 2020).”
Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2 (2020, background): “Three recent cryoelectron microscopy (cryo-EM) studies demonstrated that SARS-CoV-2 spike protein directly binds to ACE2, and the SARS-CoV-2 spike protein recognizes human ACE2 with even higher binding affinity than Spike from SARSCoV (Walls et al., 2020; Wan et al., 2020; Wrapp et al., 2020).”