scholarly journals Regional Variant Analysis of Spike Glycoprotein Mutations of SARS-CoV-2 and Its Implications in COVID-19 Pandemic Control

2021 ◽  
Author(s):  
Naseef Punnoth Poonkuzhi ◽  
Muhammed Elayadeth-Meethal ◽  
Shyju Ollakkot ◽  
Ilyas UK ◽  
Mohamed Saheer Kuruniyan
Keyword(s):  
Host Range ◽  
Receptor Binding ◽  
Topological Analysis ◽  
Interaction Network ◽  
Spike Protein ◽  
Spike Glycoprotein ◽  
Residue Interaction ◽  
Binding Antibody ◽  
Glycoprotein Structure ◽  
Variant Analysis

Mutations in the spike glycoprotein have various impacts on the receptor binding, antibody in-teraction, and host range of SARS-CoV-2. As the interaction of spike glycoprotein with the human ACE2 receptor is the entry point of SARS-CoV-2 in human cells, mutations in the spike protein it-self contain numerous impacts on the pandemic. Here, we analysed all the mutations in the spike glycoprotein from123 strains isolated from Kerala, India. We also predicted the possible struc-tural relevance of the unique mutations based on topological analysis of the residue interaction network of the spike glycoprotein structure.

scholarly journals Investigation of interaction between close and open types of SARS-Cov-2 spike glycoprotein with synthesized and natural Compounds as inhibitor; Molecular Docking Study

2020 ◽  
Author(s):  
Masume Jomhori ◽  
Hamid Mosaddeghi
Keyword(s):  
Binding Site ◽  
Receptor Binding ◽  
Antiviral Drug ◽  
Severe Infection ◽  
Docking Study ◽  
Spike Protein ◽  
Spike Glycoprotein ◽  
Molecular Docking Study ◽  
Antiviral Compound ◽  
Pubchem Database

Abstract Purpose Viral diseases are increasingly endangering universal public health because of a shortage of successful antiviral therapies. The novel pandemic 2019 n-Cov2 disease (COVID-19) is recently identified as viral disorder triggered by a new type of coronavirus. This type of coronavirus binds to the host human receptors through the Spike glycoprotein(S) Receptor Binding Domain (RBD). Two types of spike protein have been identified in open and closed states in which the open type causes severe infection. Thus, this receptor is a significant target for antiviral drug design.Methods Totally 111*2 natural and synthetic compounds were chosen from the PubChem database as ligands. To recognize the ability of direct contact between ligands and the binding site of 2019 n-Cov 2 -ACE2 protein, we have docked all compounds to the protein using AutoDock Vina. The FaF3-Drugs, Pan Assay Intrusion Compounds (PAINS), absorption, distribution, metabolism, excretion (ADME) and Lipinski's rules were used to evaluate the drug-like properties of the identified ligands. Antiviral compound prediction (AVC pred) also was used to assess antivirus properties.Results The results showed that seven ligands out of all had interactions with spike protein-angiotensin converting enzyme 2 binding site. We have found that six out of seven ligands show drug-like characteristics. We also found that the fluorophenyl and propane groups of ligands had the best interaction with the binding site of the protein.Conclusion Further, our results showed the ability of these ligands to prevent receptor binding of the spike protein SARS-CoV-2, so they would be considered as novel compounds of COVID-19 therapy drugs.

scholarly journals SARS-CoV-2 variants of concern Alpha, Beta, Gamma and Delta have extended ACE2 receptor host-ranges

2021 ◽  
Author(s):  
Nazia Thakur ◽  
Giulia Gallo ◽  
Joseph Newman ◽  
Thomas P Peacock ◽  
Luca Biasetti ◽  
...  
Keyword(s):  
Public Health ◽  
Host Range ◽  
Receptor Binding ◽  
Immune Escape ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Public Health Perspective ◽  
Global Prevalence ◽  
Usage Patterns ◽  
Alpha Beta

Following the emergence of SARS-CoV-2 in China in late 2019 a number of variants have emerged, with two of these, Alpha and Delta, subsequently growing to global prevalence. One characteristic of these variants are changes within the Spike protein, in particular the receptor binding domain (RBD). From a public health perspective these changes have important implications for increased transmissibility and immune escape; however, their presence could also modify the intrinsic host-range of the virus. Using viral pseudotyping we examined whether the variants of concern (VOCs) Alpha, Beta, Gamma and Delta have differing host ACE2 receptor usage patterns, focusing on a range of relevant mammalian ACE2 proteins. All four VOCs were able to overcome a previous restriction for mouse ACE2, with demonstrable differences also seen for individual VOCs with rat, ferret or civet ACE2 receptors, changes which we subsequently attribute to N501Y and E484K substitutions within the Spike RBD.

scholarly journals TARGETING SPIKE PROTEIN OF SARS-COV-2 FOR DEVELOPMENT OF COVID-19 VACCINES AND THERAPEUTICS

2020 ◽  
Vol 8 (Spl-1-SARS-CoV-2) ◽  
pp. S45-S56
Author(s):  
G. N. Tanuj ◽  
◽  
Anandu S. ◽  
Khan Sharun ◽  
Kuldeep Dhama ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Viral Vector ◽  
Spike Protein ◽  
Viral Fusion ◽  
T Cell Epitopes ◽  
Spike Glycoprotein ◽  
Food Market ◽  
Novel Coronavirus ◽  
And Control

Coronavirus disease 2019 (COVID-19) was first reported in the sea-food market of Wuhan, China which and later declared as a pandemic. The novel coronavirus responsible for COVID-19 was later given the name severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) due to its close similarity with SARS-CoV. The entry of the virus is mediated through the interaction of spike glycoprotein with the host receptor angiotensin-converting enzyme 2 (ACE2). The Spike protein plays a pivotal role in SARS-CoV-2 infection as it is required for both receptor binding and viral fusion, hence the key target for neutralizing antibodies. Owing to its important role, Spike protein stands as the prime target for developing vaccines and therapeutics. The S glycoprotein carries the receptor-binding domain and the major B cell and T cell epitopes, which indicate that it is a potential target for vaccines and therapeutics. Several candidate vaccines have already entered into the clinical trials. The commonly employed vaccine platforms for COVID-19 include subunit, virus-like particles (VLPs), DNA, RNA, and viral vector-based platforms. The majority of these vaccine candidates target the Spike glycoprotein to elicit an efficient immune response. The safety profile and clinical efficacy of COVID-19 vaccines that are currently under trials are quite reassuring, but it is still way ahead from attaining commercial utility. In this review, we have highlighted the recent advances in S protein-based vaccine and anti-viral platforms along with their importance in prophylaxis and control of COVID-19.

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

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.

scholarly journals Identification of the Receptor-Binding Domain of the Spike Glycoprotein of Human Betacoronavirus HKU1

2015 ◽  
Vol 89 (17) ◽  
pp. 8816-8827 ◽  
Author(s):  
Zhaohui Qian ◽  
Xiuyuan Ou ◽  
Luiz Gustavo Bentim Góes ◽  
Christina Osborne ◽  
Anna Castano ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Hepatitis Virus ◽  
Mouse Hepatitis Virus ◽  
Binding Domain ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Spike Glycoprotein ◽  
S Protein ◽  
Receptor Proteins ◽  
Group A

ABSTRACTCoronavirus spike (S) glycoproteins mediate receptor binding, membrane fusion, and virus entry and determine host range. Murine betacoronavirus (β-CoV) in group A uses the N-terminal domain (NTD) of S protein to bind to its receptor, whereas the β-CoVs severe acute respiratory syndrome CoV in group B and Middle East respiratory syndrome CoV in group C and several α-CoVs use the downstream C domain in their S proteins to recognize their receptor proteins. To identify the receptor-binding domain in the spike of human β-CoV HKU1 in group A, we generated and mapped a panel of monoclonal antibodies (MAbs) to the ectodomain of HKU1 spike protein. They did not cross-react with S proteins of any other CoV tested. Most of the HKU1 spike MAbs recognized epitopes in the C domain between amino acids 535 and 673, indicating that this region is immunodominant. Two of the MAbs blocked HKU1 virus infection of primary human tracheal-bronchial epithelial (HTBE) cells. Preincubation of HTBE cells with a truncated HKU1 S protein that includes the C domain blocked infection with HKU1 virus, but preincubation of cells with truncated S protein containing only the NTD did not block infection. These data suggest that the receptor-binding domain (RBD) of HKU1 spike protein is located in the C domain, where the spike proteins of α-CoVs and β-CoVs in groups B and C bind to their specific receptor proteins. Thus, two β-CoVs in group A, HKU1 and murine CoV, have evolved to use different regions of their spike glycoproteins to recognize their respective receptor proteins.IMPORTANCEMouse hepatitis virus, a β-CoV in group A, uses the galectin-like NTD in its spike protein to bind its receptor protein, while HCoV-OC43, another β-CoV in group A, uses the NTD to bind to its sialic-acid containing receptor. In marked contrast, the NTD of the spike glycoprotein of human respiratory β-CoV HKU1, which is also in group A, does not bind sugar. In this study, we showed that for the spike protein of HKU1, the purified C domain, downstream of the NTD, could block HKU1 virus infection of human respiratory epithelial cells, and that several monoclonal antibodies that mapped to the C domain neutralized virus infectivity. Thus, the receptor-binding domain of HKU1 spike glycoprotein is located in the C domain. Surprisingly, two β-CoVs in group A, mouse hepatitis virus and HKU1, have evolved to use different regions of their spike glycoproteins to recognize their respective receptors.

scholarly journals Identification of IgG antibody response to SARS-CoV-2 spike protein and its receptor binding domain does not predict rapid recovery from COVID-19

2020 ◽  
Author(s):  
Kathleen M. McAndrews ◽  
Dara P. Dowlatshahi ◽  
Janine Hensel ◽  
Luis L. Ostrosky-Zeichner ◽  
Ramesh Papanna ◽  
...  
Keyword(s):  
Health Care ◽  
Antibody Response ◽  
Receptor Binding ◽  
Binding Domain ◽  
Spike Protein ◽  
Quantitative Detection ◽  
Receptor Binding Domain ◽  
Igg Antibodies ◽  
Spike Glycoprotein ◽  
The World

AbstractDiagnostic testing and evaluation of patient immunity against the novel severe acute respiratory syndrome (SARS) corona virus that emerged last year (SARS-CoV-2) are essential for health and economic crisis recovery of the world. It is suggested that potential acquired immunity against SARS-CoV-2 from prior exposure may be determined by detecting the presence of circulating IgG antibodies against viral antigens, such as the spike glycoprotein and its receptor binding domain (RBD). Testing our asymptomatic population for evidence of COVID-19 immunity would also offer valuable epidemiologic data to aid health care policies and health care management. Currently, there are over 100 antibody tests that are being used around the world without approval from the FDA or similar regulatory bodies, and they are mostly for rapid and qualitative assessment, with different degrees of error rates. ELISA-based testing for sensitive and rigorous quantitative assessment of SARS-CoV-2 antibodies can potentially offer mechanistic insights into the COVID-19 disease and aid communities uniquely challenged by limited financial resources and access to commercial testing products. Employing recombinant SARS-CoV-2 RBD and spike protein generated in the laboratory, we devised a quantitative ELISA for the detection of circulating serum antibodies. Serum from twenty SARS-CoV-2 RT-PCR confirmed COVID-19 hospitalized patients were used to detect circulating IgG titers against SARS-CoV-2 spike protein and RBD. Quantitative detection of IgG antibodies to the spike glycoprotein or the RBD in patient samples was not always associated with faster recovery, compared to patients with borderline antibody response to the RBD. One patient who did not develop antibodies to the RBD completely recovered from COVID-19. In surveying 99 healthy donor samples (procured between 2017-February 2020), we detected RBD antibodies in one donor from February 2020 collection with three others exhibiting antibodies to the spike protein but not the RBD. Collectively, our study suggests that more rigorous and quantitative analysis, employing large scale samples sets, is required to determine whether antibodies to SARS-CoV-2 spike protein or RBD is associated with protection from COVID-19 disease. It is also conceivable that humoral response to SARS-CoV-2 spike protein or RBD works in association with adaptive T cell response to determine clinical sequela and severity of COVID-19 disease.

scholarly journals Evolution of the SARS-CoV-2 spike protein in the human host

2021 ◽  
Author(s):  
Antoni Wrobel ◽  
Donald Benton ◽  
Chloë Roustan ◽  
Annabel Borg ◽  
Saira Hussain ◽  
...  
Keyword(s):  
Structural Change ◽  
Receptor Binding ◽  
Human Cells ◽  
Spike Protein ◽  
Spike Glycoprotein ◽  
Neutralising Antibodies ◽  
Binding Properties ◽  
Human Host ◽  
Binding Domains ◽  
The Uk

Abstract Variants of SARS-CoV-2 have emerged which contain multiple substitutions in the surface spike glycoprotein that have been associated with increased transmission and resistance to neutralising antibodies and antisera. We have examined the structure and receptor binding properties of spike proteins from the B.1.1.7 (UK) and B.1.351 (SA) variants to better understand the evolution of the virus in humans. Both variants’ spikes have the same mutation, N501Y, in their receptor-binding domains that confers tighter ACE2 binding and this substitution relies on a common earlier substitution (D614G) to achieve the tighter binding. Each variant spike has also acquired a key change in structure that impacts virus pathogenesis. Unlike other SARS-CoV-2 spikes, the spike from the UK variant is stable against detrimerisation on binding ACE2. This feature primarily arises from the acquisition of a substitution at the S1-S2 furin site that allows for near-complete cleavage. In the SA variant spike, the presence of a new substitution, K417N, again on the background of the D614G substitution, enables the spike trimer to adopt fully open conformations that are required for receptor binding. Both types of structural change likely contribute to the increased effectiveness of these viruses for infecting human cells.

Is the Rigidity of SARS-CoV-2 Spike Receptor-Binding Motif the Hallmark for Its Enhanced Infectivity and Pathogenesis?

2020 ◽  
Author(s):  
Angelo Spinello ◽  
Andrea Saltalamacchia ◽  
Alessandra Magistrato
Keyword(s):  
Health Economic ◽  
Global Health ◽  
Receptor Binding ◽  
Binding Motif ◽  
Spike Glycoprotein ◽  
High Affinity ◽  
Global Pandemic ◽  
Medical Countermeasures ◽  
High Infectivity ◽  
Human Receptor

<p>The latest outbreak of a new pathogenic coronavirus (SARS-CoV-2) is provoking a global health, economic and societal crisis. All-atom simulations enabled us to uncover the key molecular traits underlying the high affinity of SARS-CoV-2 spike glycoprotein towards its human receptor, providing a rationale to its high infectivity. Harnessing this knowledge can boost developing effective medical countermeasures to fight the current global pandemic.</p>

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).

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