Structure and binding properties of Pangolin-CoV Spike glycoprotein inform the evolution of SARS-CoV-2.

Abstract Coronaviruses of bats and pangolins are implicated in the origin and evolution of the pandemic SARS-CoV-2. We show that Spikes from Pangolin-CoVs, closely related to SARS-CoV-2, bind strongly to human and pangolin ACE2 receptors. We also report Cryo-EM structure of Pangolin-CoV S and show it adopts a fully-closed conformation and that, aside from the Receptor-Binding Domain, it resembles the spike of a bat coronavirus RaTG13 more than that of SARS-CoV-2.

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Structure and binding properties of Pangolin-CoV spike glycoprotein inform the evolution of SARS-CoV-2

Nature Communications ◽

10.1038/s41467-021-21006-9 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Antoni G. Wrobel ◽

Donald J. Benton ◽

Pengqi Xu ◽

Lesley J. Calder ◽

Annabel Borg ◽

...

Keyword(s):

Receptor Binding ◽

Binding Domain ◽

Spike Protein ◽

Receptor Binding Domain ◽

Spike Glycoprotein ◽

Binding Properties ◽

Origin And Evolution ◽

Closed Conformation ◽

Bat Coronavirus

AbstractCoronaviruses of bats and pangolins have been implicated in the origin and evolution of the pandemic SARS-CoV-2. We show that spikes from Guangdong Pangolin-CoVs, closely related to SARS-CoV-2, bind strongly to human and pangolin ACE2 receptors. We also report the cryo-EM structure of a Pangolin-CoV spike protein and show it adopts a fully-closed conformation and that, aside from the Receptor-Binding Domain, it resembles the spike of a bat coronavirus RaTG13 more than that of SARS-CoV-2.

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Identification of a SARS-like bat coronavirus that shares structural features with the spike glycoprotein receptor-binding domain of SARS-CoV-2

Access Microbiology ◽

10.1099/acmi.0.000166 ◽

2020 ◽

Vol 2 (11) ◽

Author(s):

Conchita Fraguas Bringas ◽

David Booth

Keyword(s):

Receptor Binding ◽

Structural Features ◽

Binding Domain ◽

Receptor Binding Domain ◽

Spike Glycoprotein ◽

Angiotensin Converting Enzyme 2 ◽

Reliable Model ◽

High Conservation ◽

Host Range Determination ◽

Bat Coronavirus

SARS-CoV-2 is a recently emerged coronavirus that binds angiotensin-converting enzyme 2 (ACE2) for cell entry via its receptor-binding domain (RBD) on a surface-expressed spike glycoprotein. Studies show that despite its similarities to severe acute respiratory syndrome (SARS) coronavirus, there are critical differences in key RBD residues when compared to SARS-CoV-2. Here we present a short in silico study, showing that SARS-like bat coronavirus Rs3367 shares a high conservation with SARS-CoV-2 in important RBD residues for ACE2 binding: SARS-CoV-2’s Phe486, Thr500, Asn501 and Tyr505; implicated in receptor-binding strength and host-range determination. These features were not shared with other studied bat coronaviruses belonging to the betacoronavirus genus, including RaTG13, the closest reported bat coronavirus to SARS-CoV-2’s spike protein. Sequence and phylogeny analyses were followed by the computation of a reliable model of the RBD of SARS-like bat coronavirus Rs3367, which allowed structural insight of the conserved residues. Superimposition of this model on the SARS-CoV-2 ACE2-RBD complex revealed critical ACE2 contacts are also maintained. In addition, residue Asn488Rs3367 interacted with a previously defined pocket on ACE2 composed of Tyr41, Lys353 and Asp355. When compared to available SARS-CoV-2 crystal structure data, Asn501SARS-CoV-2 showed a different interaction with the ACE2 pocket. Taken together, this study offers molecular insights on RBD-receptor interactions with implications for vaccine design.

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Role of key point Mutations in Receptor Binding Domain of SARS-CoV-2 Spike Glycoprotein

Infectious Disorders - Drug Targets ◽

10.2174/1871526520666200804161650 ◽

2020 ◽

Vol 20 ◽

Author(s):

Bipin Singh

Keyword(s):

Receptor Binding ◽

Point Mutations ◽

Binding Domain ◽

Receptor Binding Domain ◽

Spike Glycoprotein ◽

Angiotensin Converting Enzyme 2 ◽

Recent Outbreak ◽

Novel Coronavirus ◽

Genomic Similarity

: The recent outbreak of novel coronavirus (SARS-CoV-2 or 2019-nCoV) and its worldwide spread is posing one of the major threats to human health and the world economy. It has been suggested that SARS-CoV-2 is similar to SARSCoV based on the comparison of the genome sequence. Despite the genomic similarity between SARS-CoV-2 and SARSCoV, the spike glycoprotein and receptor binding domain in SARS-CoV-2 shows the considerable difference compared to SARS-CoV, due to the presence of several point mutations. The analysis of receptor binding domain (RBD) from recently published 3D structures of spike glycoprotein of SARS-CoV-2 (Yan, R., et al. (2020); Wrapp, D., et al. (2020); Walls, A. C., et al. (2020)) highlights the contribution of a few key point mutations in RBD of spike glycoprotein and molecular basis of its efficient binding with human angiotensin-converting enzyme 2 (ACE2).

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Structural Definition of a Unique Neutralization Epitope on the Receptor-Binding Domain of MERS-CoV Spike Glycoprotein

Cell Reports ◽

10.1016/j.celrep.2018.06.041 ◽

2018 ◽

Vol 24 (2) ◽

pp. 441-452 ◽

Cited By ~ 30

Author(s):

Senyan Zhang ◽

Panpan Zhou ◽

Pengfei Wang ◽

Yangyang Li ◽

Liwei Jiang ◽

...

Keyword(s):

Receptor Binding ◽

Binding Domain ◽

Receptor Binding Domain ◽

Spike Glycoprotein ◽

Neutralization Epitope ◽

Definition Of ◽

Structural Definition

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Discovery of potential inhibitors of the receptor-binding domain (RBD) of pandemic disease-causing SARS-CoV-2 Spike Glycoprotein from Triphala through molecular docking

Current Chinese Chemistry ◽

10.2174/2666001601666210322121802 ◽

2021 ◽

Vol 01 ◽

Author(s):

Sharuk L. Khan ◽

Falak A. Siddiqui ◽

Mohd Sayeed Shaikh ◽

Nitin V. Nema ◽

Aijaz A. Shaikh

Keyword(s):

Molecular Docking ◽

Hydrogen Bonds ◽

Receptor Binding ◽

Chemical Constituents ◽

Antioxidant Properties ◽

Binding Domain ◽

Quality Data ◽

Receptor Binding Domain ◽

Spike Glycoprotein

Background: COVID-19 (SARS-CoV-2 infection) has affected almost every region of the world. Presently, there is no defined line of treatment available for it. Triphala is already proven to have a safe biological window and well known for its antioxidant and immunomodulatory properties. Objective: Present work has been carried out to study Triphala's effectiveness for the treatment of COVID-19. Methods: The Receptor-binding domain (RBD) of SARS-CoV-2 Spike Glycoprotein responsible for the invasion into the host cell, which leads to further infection. The molecular docking (MD) was performed to explore the binding affinities (kcal/mol) of Triphala's chemical constituents and compared them with the existing drugs under investigation for the treatment of COVID-19 epidemiology. Results: Chebulinic acid binding affinity -8.5 kcal/mol with the formation of 10 hydrogen bonds. Almost all the major chemical constituents have formed two or more hydrogen bonds with RBD of SARS-CoV-2 Spike Glycoprotein. Conclusion: The present study showed that Triphala might perform vital roles in the treatment of COVID-19 and expand its usefulness to physicians to treat this illness. There is a need to complete the in-vitro, in-vivo biological testing of Triphala on SARS-CoV-2 disease to create more quality data. The binding mode of Chebulinic acid in the allosteric cavity allows a better understanding of RBD of SARS-CoV-2 Spike Glycoprotein target and provides insight for the design of new inhibitors. Triphala is already proven to have a safe biological window, which indicates we can skip the pre-clinical trials. Apart from this, Triphala is well known for its antioxidant properties, which ultimately improves the immunity of the COVID-19 patient.

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Computational Approach Revealed Potential Affinity of Antiasthmatics Against Receptor Binding Domain of 2019n-Cov Spike Glycoprotein

10.26434/chemrxiv.12115638.v1 ◽

2020 ◽

Author(s):

LAMIAE ELKHATTABI ◽

Hicham Charoute ◽

Rachid Saile ◽

Abdelhamid Barakat

Keyword(s):

Molecular Docking ◽

Receptor Binding ◽

In Silico ◽

Cyclic Peptide ◽

Direct Interaction ◽

Binding Domain ◽

Binding Energies ◽

Receptor Binding Domain ◽

Spike Glycoprotein ◽

Pubchem Database

The novel COVID-19 pandemic is now a health threat, with a deep-felt impact worldwide. The new coronavirus 2019 (2019 n-Cov) binds to host human receptors through Receptor Binding Domain RBD of Spike glycoprotein (S), making it a prominent drug target. The present study aims to identify new potential hits that can inhibit the S protein using in silico approaches. Several natural and synthetics compounds (antiasthmatics, Antiviral, Antimalarial, Antibacterial, Anti-Inflammatory, cyclic peptide, and cyclic bis) were screened by molecular docking using AutoDock Vina. Additionally, we tested calcitriol and three known drugs (Azithromycin, HydroxyChloroquine, and Chloroquine ) against the spike protein to found if they have any direct interaction.<br>Our finding consists of 4 potential synthetic compounds from PubChem database, known for their antiasthmatic effects, that show highly binding energies each (-8.6 kcal/mol, 7.7kcal/mol, -7.2 kcal/mol and -7.0 kcal/mol). Another 5 natural compounds from the South African natural sources database (SANCDB) that bind to RBD of Spike with significant energy each: (Marchantin C with -7.3 kcal/mol, Riccardin C with -7.0 kcal/mol, Digitoxigenin-glucoside with -6.9 kcal/mol, D-Friedoolean-14-en-oic acid with -6.8 kcal/mol and, Spongotine A with -6.7 kcal/mol). The FaF-Drugs server was used to evaluate the drug-like properties of the identified compounds. Additionally, Calcitriol, Azithromycin, and HydroxyChloroquine have an appreciable binding affinity to 2019-nCoV S, suggesting a possible mechanism of action. Using in silico approaches like molecular docking and pharmacokinetic properties, we showed new potential inhibitors. Our findings need further analysis, and chemical design for more effective derivatives of these compounds speculated to disrupt the viral recognition of host receptors.

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Crystallization and Structural Determination of the Receptor-Binding Domain of MERS-CoV Spike Glycoprotein

Methods in Molecular Biology - MERS Coronavirus ◽

10.1007/978-1-0716-0211-9_4 ◽

2019 ◽

pp. 39-50

Author(s):

Haixia Zhou ◽

Shuyuan Zhang ◽

Xinquan Wang

Keyword(s):

Receptor Binding ◽

Binding Domain ◽

Structural Determination ◽

Receptor Binding Domain ◽

Spike Glycoprotein

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Antiviral Drug Design Based on the Opening Mechanism of Spike Glycoprotein in SARS-CoV-2

Physical Chemistry Chemical Physics ◽

10.1039/d1cp01045j ◽

2021 ◽

Author(s):

Ruichao Mao ◽

Lihua Bie ◽

Maofeng Xu ◽

Xiaocong Wang ◽

Jun Gao

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Drug Design ◽

Host Cell ◽

Receptor Binding ◽

Antiviral Drug ◽

Binding Domain ◽

The Novel ◽

Receptor Binding Domain ◽

Spike Glycoprotein

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the host cell after the receptor binding domain (RBD) of the virus spike (S) glycoprotein binding to the human angiotensin-converting...

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Identification of a Receptor-Binding Domain of the Spike Glycoprotein of Human Coronavirus HCoV-229E

Journal of Virology ◽

10.1128/jvi.77.4.2530-2538.2003 ◽

2003 ◽

Vol 77 (4) ◽

pp. 2530-2538 ◽

Cited By ~ 111

Author(s):

Aurelio Bonavia ◽

Bruce D. Zelus ◽

David E. Wentworth ◽

Pierre J. Talbot ◽

Kathryn V. Holmes

Keyword(s):

Amino Acids ◽

Receptor Binding ◽

Protein A ◽

Binding Domain ◽

Expression Vectors ◽

Receptor Binding Domain ◽

3T3 Cells ◽

Spike Glycoprotein ◽

Human Coronavirus ◽

S Proteins

ABSTRACT Human coronavirus HCoV-229E uses human aminopeptidase N (hAPN) as its receptor (C. L. Yeager et al., Nature 357:420-422, 1992). To identify the receptor-binding domain of the viral spike glycoprotein (S), we expressed soluble truncated histidine-tagged S glycoproteins by using baculovirus expression vectors. Truncated S proteins purified by nickel affinity chromatography were shown to be glycosylated and to react with polyclonal anti-HCoV-229E antibodies and monoclonal antibodies to the viral S protein. A truncated protein (S547) that contains the N-terminal 547 amino acids bound to 3T3 mouse cells that express hAPN but not to mouse 3T3 cells transfected with empty vector. Binding of S547 to hAPN was blocked by an anti-hAPN monoclonal antibody that inhibits binding of virus to hAPN and blocks virus infection of human cells and was also blocked by polyclonal anti-HCoV-229E antibody. S proteins that contain the N-terminal 268 or 417 amino acids did not bind to hAPN-3T3 cells. Antibody to the region from amino acid 417 to the C terminus of S blocked binding of S547 to hAPN-3T3 cells. Thus, the data suggest that the domain of the spike protein between amino acids 417 and 547 is required for the binding of HCoV-229E to its hAPN receptor.

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