scholarly journals Human serum from SARS-CoV-2 vaccinated and COVID-19 patients shows reduced binding to the RBD of SARS-CoV-2 Omicron variant in comparison to the original Wuhan strain and the Beta and Delta variants

2021 ◽  
Author(s):  
Maren Schubert ◽  
Federico Bertoglio ◽  
Stephan Steinke ◽  
Philip Alexander Heine ◽  
Mario Alberto Ynga-Durand ◽  
...  
Keyword(s):  
Amino Acid ◽  
Receptor Binding ◽  
Insect Cells ◽  
The Other ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Boost Vaccine ◽  
Human Sera ◽  
Life Threatening ◽  
Asymptomatic Infections

Background The ongoing COVID-19 pandemic is caused by the beta coronavirus SARS-CoV-2. COVID-19 manifests itself from mild or even asymptomatic infections to severe forms of life-threatening pneumonia. At the end of November 2021, yet another novel SARS-CoV-2 variant named B.1.1.529 or Omicron was discovered and classified as a variant of concern (VoC) by the WHO. Omicron shows significantly more mutations in the amino acid (aa) sequence of its spike protein than any previous variant, with the majority of those concentrated in the receptor binding domain (RBD). In this work, the binding of the Omicron RBD to the human ACE2 receptor was experimentally analyzed in comparison to the original Wuhan SARS-CoV-2 virus, and the Beta and Delta variants. Moreover, we compared the ability of human sera from COVID-19 convalescent donors and persons fully vaccinated with BNT162b2 (Corminaty) or Ad26.COV2.S (Janssen COVID-19 vaccine) as well as individuals who had boost vaccine doses with BNT162b2 or mRNA-1273 (Spikevax) to bind the different RBDs variants. Methods The Omicron RBD with 15 aa mutations compared to the original Wuhan strain was produced baculovirus-free in insect cells. Binding of the produced Omicron RBD to hACE was analyzed by ELISA. Sera from 27 COVID-19 patients, of whom 21 were fully vaccinated and 16 booster recipients were titrated on the original Wuhan strain, Beta, Delta and Omicron RBD and compared to the first WHO International Standard for anti-SARS-CoV-2 immunoglobulin (human) using the original Wuhan strain as reference. Results The Omicron RBD showed a slightly reduced binding to ACE2 compared to the other RBDs. The serum of COVID-19 patients, BNT162b2 vaccinated and boost vaccinated persons showed a reduced binding to Omicron RBD in comparison to the original Wuhan strain, Beta und Delta RBDs. In this assay, the boost vaccination did not improve the RBD binding when compared to the BNT162b2 fully vaccinated group. The RBD binding of the Ad26.COV2.S serum group was lower at all compared to the other groups. Conclusions The reduced binding of human sera to Omicron RBD provides first hints that the current vaccinations using BNT162b2, mRNA-1273 and Ad26.COV2.S may be less efficient in preventing infections with the Omicron variant.

ReaxFF-based molecular dynamics simulation of the interaction between plasma ROS and the receptor-binding domain of the spike protein in the capsid protein of SARS-CoV-2

2021 ◽  
Author(s):  
Huichao Wang ◽  
Tong Zhao ◽  
Shuhui Yang ◽  
Liang Zou ◽  
Xiaolong Wang ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Amino Acid ◽  
Capsid Protein ◽  
Receptor Binding ◽  
Hydrogen Abstraction ◽  
Binding Domain ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Amino Acid Residues ◽  
Global Epidemic

Abstract Under the severe situation of the current global epidemic, researchers have been working hard to find a reliable way to suppress the infection of the virus and prevent the spread of the epidemic. Studies have shown that the recognition and binding of human angiotensin-converting enzyme 2 (ACE2) by the receptor-binding domain (BRD) of spike protein on the surface of SARS-CoV-2 is a crucial step for SARS-CoV-2 to invade human receptor cells, and blocking this process can inhibit the virus from invading human normal cells. Plasma treatment can disrupt the structure of the RBD and effectively block the binding process. However, the mechanism by which plasma blocks the recognition and binding between the two is not clear. In this study, reaction process between reactive oxygen species (ROS) in plasma and the molecular model of RBD was simulated using a reactive molecular dynamics method. The results showed that the destruction of RBD molecule by ROS was triggered by hydrogen abstraction reactions. O and OH abstracted H atoms from RBD, while the H atoms of H2O2 and HO2 were abstracted by RBD. The hydrogen abstraction resulted in the breakage of C-H, N-H, O-H and C=O bonds and the formation of C=C, C=N bonds. The addition reaction of OH increased the number of O-H bonds and caused the formation of C-O, N-O and O-H bonds. The dissociation of N-H bonds led to the destruction of the original structure of peptide bonds and amino acid residues, change the type of amino acid residues, and caused the conversion of N-C and N=C, C=O and C-O. The simulation partially elucidated the microscopic mechanism of the interaction between ROS in plasma and the capsid protein of SARS-CoV-2, providing theoretical support for the control of SARS-CoV-2 infection by plasma, a contribution to overcoming the global epidemic problem.

Construction and immunogenic studies of a mFc fusion receptor binding domain (RBD) of spike protein as a subunit vaccine against SARS-CoV-2 infection

2020 ◽  
Vol 56 (61) ◽  
pp. 8683-8686 ◽  
Author(s):  
Xiaoxiao Qi ◽  
Bixia Ke ◽  
Qian Feng ◽  
Deying Yang ◽  
Qinghai Lian ◽  
...  
Keyword(s):  
Amino Acid ◽  
Fusion Protein ◽  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Subunit Vaccine ◽  
Binding Domain ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Humoral And Cellular Immunity ◽  
A Subunit

Herein, we report that a recombinant fusion protein, containing a 457 amino acid SARS-CoV-2 receptor binding domain and a mouse IgG1 Fc domain, could induce highly potent neutralizing antibodies and stimulate humoral and cellular immunity in mice.

scholarly journals A Potential SARS-CoV-2 Variant of Interest (VOI) Harboring Mutation E484K in the Spike Protein Was Identified within Lineage B.1.1.33 Circulating in Brazil

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 724
Author(s):  
Paola Cristina Resende ◽  
Tiago Gräf ◽  
Anna Carolina Dias Paixão ◽  
Luciana Appolinario ◽  
Renata Serrano Lopes ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Receptor Binding ◽  
Binding Domain ◽  
The Other ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
S Protein ◽  
Other Hand

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic in Brazil was dominated by two lineages designated as B.1.1.28 and B.1.1.33. The two SARS-CoV-2 variants harboring mutations at the receptor-binding domain of the Spike (S) protein, designated as lineages P.1 and P.2, evolved from lineage B.1.1.28 and are rapidly spreading in Brazil. Lineage P.1 is considered a Variant of Concern (VOC) because of the presence of multiple mutations in the S protein (including K417T, E484K, N501Y), while lineage P.2 only harbors mutation S:E484K and is considered a Variant of Interest (VOI). On the other hand, epidemiologically relevant B.1.1.33 deriving lineages have not been described so far. Here we report the identification of a new SARS-CoV-2 VOI within lineage B.1.1.33 that also harbors mutation S:E484K and was detected in Brazil between November 2020 and February 2021. This VOI displayed four non-synonymous lineage-defining mutations (NSP3:A1711V, NSP6:F36L, S:E484K, and NS7b:E33A) and was designated as lineage N.9. The VOI N.9 probably emerged in August 2020 and has spread across different Brazilian states from the Southeast, South, North, and Northeast regions.

scholarly journals Analyses of spike protein from first deposited sequences of SARS-CoV2 from West Bengal, India

2020 ◽  
Author(s):  
Feroza Begum ◽  
Debica Mukherjee ◽  
Dluya Thagriki ◽  
Sandeepan Das ◽  
Prem Prakash Tripathi ◽  
...  
Keyword(s):  
Receptor Binding ◽  
West Bengal ◽  
Protein Sequences ◽  
Complete Sequence ◽  
The Other ◽  
Host Cells ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Eastern India ◽  
Global Initiative

AbstractIndia has recently started sequencing SARS-CoV2 genome from clinical isolates. Currently only few sequences are available from three states in India. Kerala was the first state to deposit complete sequence from two isolates followed by one from Gujarat. On April 27, 2020, the first five sequences from the state of West Bengal (Eastern India) were deposited on ‘a global initiative on sharing avian flu data’ (GISAID) platform. In this paper we have analysed the spike protein sequences from all these five isolates and also compared for their similarities or differences with other sequences reported in India and with isolates of Wuhan origin. We report one unique mutation at position 723 and the other at 1124 in the S2 domain of spike protein of the isolates from West Bengal only and one mutation downstream of the receptor binding domain at position 614 in S1 domain which was common with the sequence from Gujarat (a state of western part of India). Mutation in the S2 domain showed changes in the secondary structure of the spike protein at region of mutation. We also studied molecular dynamics using normal mode analyses and found that this mutation decreases the flexibility of S2 domain. Since both S1 and S2 are important in receptor binding followed by entry in the host cells, such mutations may define the affinity or avidity of receptor binding.

scholarly journals Amino acid interacting network in the receptor-binding domain of SARS-CoV-2 spike protein

RSC Advances ◽  
2020 ◽  
Vol 10 (65) ◽  
pp. 39831-39841
Author(s):  
Puja Adhikari ◽  
Wai-Yim Ching
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Receptor Binding ◽  
Nearest Neighbor ◽  
Binding Domain ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Non Local

Gly504 interacting with two nearest neighbor and one non-local amino acids.

scholarly journals A Novel Real-Time RT-PCR-Based Methodology for the Preliminary Typing of SARS-CoV-2 Variants, Employing Non-Extendable LNA Oligonucleotides and Three Signature Mutations at the Spike Protein Receptor-Binding Domain

Life ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1015
Author(s):  
Serafeim C. Chaintoutis ◽  
Taxiarchis Chassalevris ◽  
Sofia Balaska ◽  
Evangelia Mouchtaropoulou ◽  
George Tsiolas ◽  
...  
Keyword(s):  
Amino Acid ◽  
Real Time ◽  
Receptor Binding ◽  
Binding Domain ◽  
Locked Nucleic Acid ◽  
Spike Protein ◽  
Amino Acid Substitutions ◽  
Receptor Binding Domain ◽  
Rt Pcr ◽  
Protein Receptor

Mutations resulting in amino-acid substitutions of the SARS-CoV-2 spike protein receptor-binding domain (RBD) have been associated with enhanced transmissibility and immune escape of the respective variants, namely Alpha, Beta, Gamma or Delta. Rapid identification of the aforementioned variants of concern and their discrimination of other variants is thus of importance for public health interventions. For this reason, a one-step real-time RT-PCR assay employing four locked nucleic acid (LNA) modified TaqMan probes was developed, to target signature mutations associated with amino-acid substitutions at positions 478, 484 and 501 present in the receptor-binding motif (RBM) of the spike protein RBD. This region contains most contacting residues of SARS-CoV-2 that bind to ACE2. A novel strategy employing the use of non-extendable LNA oligonucleotide blockers that can reduce non-specific hybridization of probes increased the number of different mutated sites examined in a multiplex PCR. The combinatory analysis of the different fluorescence signals obtained enabled the preliminary differentiation of SARS-CoV-2 variants of concern. The assay is sensitive with a LOD of 263 copies/reaction for the Delta variant, 170 copies/reaction for the Beta variant, amplification efficiencies > 91% and a linear range of >5 log10 copies/reaction against all targets. Validation of the assay using known SARS-CoV-2-positive and negative samples from humans and animals revealed its ability to correctly identify the targeted mutations and preliminary characterize the SARS-CoV-2 variants. The novel approach for mutation typing using LNA oligonucleotide blockers can be modified to target signature mutations at four different sites in the RBM and further expand the range of variants detected.

scholarly journals Proteolytic Transformation and Stimulation of SARSCov-2 Spike Protein with Human ACE-2 Receptor

2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Sohail S ◽  
◽  
Rana H ◽  
Awan DS ◽  
Sohail F ◽  
...  
Keyword(s):  
Amino Acid ◽  
Receptor Binding ◽  
Viral Entry ◽  
Attachment Site ◽  
Binding Domain ◽  
Host Cells ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Major Pathway ◽  
Important Relationship

Severe acute respiratory syndrome coronavirus has a great role in causing respiratory illness in humans and has the most important relationship of its spike proteins with host ACE-2 receptors. After entry into the human body, the viral S protein receptor-binding domain binds to human ACE-2 receptor. Two modes explained in this paper of an ACE-2 shedding. The shedding induces the process of viral entry to host cells by binding SARS-CoV-2 proteins. The residues of arginine and lysine in the ACE-2 receptor from 652 to 659 amino acid cleavage by ADAM17 but in TMPRSS2 the residues can be seen on amino acid from 697 to 716. Corona virus genome shows some structural proteins that are responsible for the cellular entry and facilitate the attachment of a virus to the host cell. Virus recognizes the attachment site and binds with it and enter into the cell. Spike protein is split from the cleavage site along its two subunits S1 and S2 then during this process. S2 subunit release RBD (Receptor- Binding Domain) of S1 mediated to the ACE-2. The RBD of S1 consists of 200 amino acid domains. The unknown protein B6ATI which is a neutral amino acid transporter located in ileum is the basic cause for formation of ACE-2 homodimer. In this way S1 domain provides site for another S2 domain. This leads to concealing of the ACE-2 ectodomain cleavage-sites, shedding. It prevents endocytosis of the receptor blocking a major pathway in the viral entry.

scholarly journals Self and Nonself Short Constituent Sequences of Amino Acids in the SARS-CoV-2 Proteome for Vaccine Development

COVID ◽  
2021 ◽  
Vol 1 (3) ◽  
pp. 555-574
Author(s):  
Joji M. Otaki ◽  
Wataru Nakasone ◽  
Morikazu Nakamura
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Human Proteome ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Amino Acid Residues

Current SARS-CoV-2 vaccines take advantage of the viral spike protein required for infection in humans. Considering that spike proteins may contain both “self” and “nonself” sequences (sequences that exist in the human proteome and those that do not, respectively), nonself sequences are likely to be better candidate epitopes than self sequences for vaccines to efficiently eliminate pathogenic proteins and to reduce the potential long-term risks of autoimmune diseases. This viewpoint is likely important when one considers that various autoantibodies are produced in COVID-19 patients. Here, we comprehensively identified self and nonself short constituent sequences (SCSs) of 5 amino acid residues in the proteome of SARS-CoV-2. Self and nonself SCSs comprised 91.2% and 8.8% of the SARS-CoV-2 proteome, respectively. We identified potentially important nonself SCS clusters in the receptor-binding domain of the spike protein that overlap with previously identified epitopes of neutralizing antibodies. These nonself SCS clusters may serve as functional epitopes for effective, safe, and long-term vaccines against SARS-CoV-2 infection. Additionally, analyses of self/nonself status changes in mutants revealed that the SARS-CoV-2 proteome may be evolving to mimic the human proteome. Further SCS-based proteome analyses may provide useful information to predict epidemiological dynamics of the current COVID-19 pandemic.

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