scholarly journals SARS-CoV-2 Beta Variant Substitutions Alter Spike Glycoprotein Receptor Binding Domain Structure and Stability

2021 ◽  
pp. 101371
Author(s):  
Daniel L. Moss ◽  
Jay Rappaport
Keyword(s):  
Domain Structure ◽  
Receptor Binding ◽  
Binding Domain ◽  
Receptor Binding Domain ◽  
Spike Glycoprotein ◽  
Structure And Stability

scholarly journals SARS-CoV-2 Variant of Concern Substitutions Alter Spike Glycoprotein Receptor Binding Domain Structure and Stability

2021 ◽  
Author(s):  
Daniel L Moss ◽  
Jay Rappaport
Keyword(s):  
Receptor Binding ◽  
Rapid Development ◽  
Structure And Function ◽  
Binding Domain ◽  
Amino Acid Substitutions ◽  
Receptor Binding Domain ◽  
Spike Glycoprotein ◽  
Structure And Stability ◽  
The World ◽  
And Function

The emergence of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) and the subsequent COVID-19 pandemic has significantly impacted the world not just with disease and death but also economic turmoil. The rapid development and deployment of extremely effective vaccines against SARS-CoV-2 has made the end of the pandemic a reality within reach. However, as the virus spreads it has acquired mutations; and thus, variants of concern have emerged that are more infectious and reduce the efficacy of existing vaccines. While promising efforts are underway to combat these variants, the evolutionary pressures leading to these variants are poorly understood. To that end, here we have studied the effects of three amino-acid substitutions on the structure and function of the SARS-CoV-2 spike glycoprotein receptor-binding domain found in several variants of concern such as B.1.1.7, B.1.351 and P.1 that are now circulating. We found that these substitutions alter the RBD structure and stability, as well as its ability to bind to ACE2, which may have opposing and compensatory effects. These findings provide new insights into how these Variants of Concern (VOC) may have been selected to optimize infectivity while maintaining the structure and stability of the receptor binding domain.

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

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).

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

Cell Reports ◽  
2018 ◽  
Vol 24 (2) ◽  
pp. 441-452 ◽  
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

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

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.

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

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.

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

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...

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

2003 ◽  
Vol 77 (4) ◽  
pp. 2530-2538 ◽  
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.

scholarly journals Crystal structure of the receptor binding domain of the spike glycoprotein of human betacoronavirus HKU1

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Xiuyuan Ou ◽  
Hongxin Guan ◽  
Bo Qin ◽  
Zhixia Mu ◽  
Justyna A. Wojdyla ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Receptor Binding ◽  
Binding Domain ◽  
Receptor Binding Domain ◽  
Spike Glycoprotein

scholarly journals Effect of RBD (Y453F) mutation in spike glycoprotein of SARS-CoV-2 on neutralizing IgG affinity

2021 ◽  
Author(s):  
Takuma Hayashi ◽  
Nobuo Yaegashi ◽  
Ikuo Konishi
Keyword(s):  
Monoclonal Antibodies ◽  
Structural Analysis ◽  
Severe Acute Respiratory Syndrome ◽  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Virus Disease ◽  
Three Dimensional ◽  
Binding Domain ◽  
Receptor Binding Domain ◽  
Spike Glycoprotein

AbstractBackgroundInfection with receptor binding domain (RBD) mutant (Y453F) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from farmed minks is known to widely spread among humans.MethodsWe investigated the characteristics of SARS-CoV-2 RBD Y453F mutant using three- dimensional structural analysis. We investigated the effect of the RBD Y453F mutant of SARS-CoV- 2 on neutralizing antibodies in serum derived from Corona virus Disease 2019 (COVID-19) positive patients.ResultsOur studies suggest that virus variants with RBD Y453F mutation partially escaped detection by four neutralizing monoclonal antibodies and neutralizing antibodies in serum.ConclusionsConsequently, raising a concern that infection of SARS-CoV-2 mutants that cause serious symptoms in humans may spread globally.

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