scholarly journals Identification of Novel Neutralizing Monoclonal Antibodies against SARS-CoV-2 Spike Glycoprotein

2021 ◽  
Author(s):  
Devivasha Bordoloi ◽  
Ziyang Xu ◽  
Michelle Ho ◽  
Mansi Purwar ◽  
Pratik Bhojnagarwala ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Spike Glycoprotein

scholarly journals Antibody-mediated disruption of the SARS-CoV-2 spike glycoprotein

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Antoni G. Wrobel ◽  
Donald J. Benton ◽  
Saira Hussain ◽  
Ruth Harvey ◽  
Stephen R. Martin ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Monoclonal Antibodies ◽  
Antibody Binding ◽  
Spike Glycoprotein ◽  
Cryo Electron Microscopy

Abstract The CR3022 antibody, selected from a group of SARS-CoV monoclonal antibodies for its ability to cross-react with SARS-CoV-2, has been examined for its ability to bind to the ectodomain of the SARS-CoV-2 spike glycoprotein. Using cryo-electron microscopy we show that antibody binding requires rearrangements in the S1 domain that result in dissociation of the spike.

scholarly journals Towards a solution to MERS: protective human monoclonal antibodies targeting different domains and functions of the MERS-coronavirus spike glycoprotein

2019 ◽  
Vol 8 (1) ◽  
pp. 516-530 ◽  
Author(s):  
Ivy Widjaja ◽  
Chunyan Wang ◽  
Rien van Haperen ◽  
Javier Gutiérrez-Álvarez ◽  
Brenda van Dieren ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Spike Glycoprotein ◽  
Human Monoclonal Antibodies

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.

scholarly journals Antibody-mediated disruption of the SARS-CoV-2 spike glycoprotein

2020 ◽  
Author(s):  
Antoni Wrobel ◽  
Donald Benton ◽  
Saira Hussain ◽  
Ruth Harvey ◽  
Chloë Roustan ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Antibody Binding ◽  
Spike Glycoprotein

Abstract The CR3022 antibody, selected from a group of SARS-CoV-1 monoclonal antibodies for its ability to cross-react with SARS-CoV-2, has been examined for its ability to bind to the ectodomain of the SARS-CoV-2 spike glycoprotein. Using electron cryo-microscopy we show that antibody binding requires rearrangements in the S1 domain that result in dissociation of the spike.

The neutralization potency of anti-SARS-CoV-2 therapeutic human monoclonal antibodies is retained against novel viral variants

2021 ◽  
Author(s):  
Efi Makdasi ◽  
Anat Zvi ◽  
Ron Alcalay ◽  
Tal Noy-Porat ◽  
Eldar Peretz ◽  
...  
Keyword(s):  
South Africa ◽  
Monoclonal Antibodies ◽  
Receptor Binding ◽  
Clinical Use ◽  
Receptor Binding Domain ◽  
Spike Glycoprotein ◽  
Human Monoclonal Antibodies ◽  
Wide Range ◽  
The Uk

SummaryA wide range of SARS-CoV-2 neutralizing monoclonal antibodies (mAbs) were reported to date, most of which target the spike glycoprotein and in particular its receptor binding domain (RBD) and N-terminal domain (NTD) of the S1 subunit. The therapeutic implementation of these antibodies has been recently challenged by the emerging SARS-CoV-2 variants, harboring an extensively-mutated spike versions. Consequently, the re-assessment of mAbs, previously reported to neutralize the original early-version of the virus, represents an assignment of high priority.With respect to the evolving mutations in the virus spike RBD, we evaluated the aptitude of four previously selected mAbs, targeting distinct epitopes, to bind RBD versions harboring individual mutations at positions 501, 477, 484, 439, 417 and 453. Mutations of these residues represent the prevailing worldwide distributed modifications of the RBD, previously reported to mediate escape from antibody neutralization. Additionally, the in vitro neutralization efficacies of the four RBD-specific mAbs, as well as two NTD-specific mAbs, were evaluated against two frequent SARS-CoV-2 variants of concern (VOCs): (i) the B.1.1.7 variant, emerged in the UK and (ii) the B.1.351 variant, emerged in South Africa. B.1.351, was previously suggested to escape many therapeutic mAbs, including those authorized for clinical use.The results of the present study, clearly indicate that in spite of mutation accumulation in the spike of the virus, some neutralizing mAbs preserve their potency to combat SARS-CoV-2 emerged variants. In particular, the previously reported highly potent MD65 mAb is shown to retain its ability to bind the prevalent novel viral mutations and to effectively neutralize the B.1.1.7 and B.1.351 variants of high clinical concern.

scholarly journals Effect of RBD mutations 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 ◽  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Three Dimensional ◽  
Binding Domain ◽  
Receptor Binding Domain ◽  
Spike Glycoprotein ◽  
Mutant Strains

Abstract Background: Certain mutant strains of SARS-CoV-2 are known to spread widely among humans, including the receptor binding domain (RBD) mutant, Y453F, from farmed minks, and the RBD mutant, N501Y, a mutation common to three major SARS-CoV-2 subspecies (B.1.1.7, B.1.351, and B.1.1.248). Methods: We investigated the characteristics of the RBD mutants, Y453F and N501Y, using three-dimensional structural analysis. We also investigated the effect of Y453F and N501Y on neutralizing antibodies in serum derived from COVID-19-positive patients. Results: Our results suggest that SARS-CoV-2 subspecies with the RBD mutations Y453F or N501Y partially escaped detection by 4 neutralizing monoclonal antibodies and 21 neutralizing antibodies in serums derived from COVID-19-positive patients.Conclusions: Infection with SARS-CoV-2 subspecies that cause serious symptoms in humans may spread globally.

scholarly journals Potent Neutralization of MERS-CoV by Human Neutralizing Monoclonal Antibodies to the Viral Spike Glycoprotein

2014 ◽  
Vol 6 (234) ◽  
pp. 234ra59-234ra59 ◽  
Author(s):  
L. Jiang ◽  
N. Wang ◽  
T. Zuo ◽  
X. Shi ◽  
K.-M. V. Poon ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Spike Glycoprotein ◽  
Potent Neutralization

scholarly journals Importance of Neutralizing Monoclonal Antibodies Targeting Multiple Antigenic Sites on the Middle East Respiratory Syndrome Coronavirus Spike Glycoprotein To Avoid Neutralization Escape

2018 ◽  
Vol 92 (10) ◽  
Author(s):  
Lingshu Wang ◽  
Wei Shi ◽  
James D. Chappell ◽  
M. Gordon Joyce ◽  
Yi Zhang ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Middle East ◽  
Receptor Binding ◽  
Binding Domain ◽  
Middle East Respiratory Syndrome ◽  
Health Concern ◽  
Immunoglobulin Gene ◽  
Receptor Binding Domain ◽  
Spike Glycoprotein ◽  
Antigenic Sites

ABSTRACT Middle East respiratory syndrome coronavirus (MERS-CoV) causes a highly lethal pulmonary infection with ∼35% mortality. The potential for a future pandemic originating from animal reservoirs or health care-associated events is a major public health concern. There are no vaccines or therapeutic agents currently available for MERS-CoV. Using a probe-based single B cell cloning strategy, we have identified and characterized multiple neutralizing monoclonal antibodies (MAbs) specifically binding to the receptor-binding domain (RBD) or S1 (non-RBD) regions from a convalescent MERS-CoV-infected patient and from immunized rhesus macaques. RBD-specific MAbs tended to have greater neutralizing potency than non-RBD S1-specific MAbs. Six RBD-specific and five S1-specific MAbs could be sorted into four RBD and three non-RBD distinct binding patterns, based on competition assays, mapping neutralization escape variants, and structural analysis. We determined cocrystal structures for two MAbs targeting the RBD from different angles and show they can bind the RBD only in the “out” position. We then showed that selected RBD-specific, non-RBD S1-specific, and S2-specific MAbs given prophylactically prevented MERS-CoV replication in lungs and protected mice from lethal challenge. Importantly, combining RBD- and non-RBD MAbs delayed the emergence of escape mutations in a cell-based virus escape assay. These studies identify MAbs targeting different antigenic sites on S that will be useful for defining mechanisms of MERS-CoV neutralization and for developing more effective interventions to prevent or treat MERS-CoV infections. IMPORTANCE MERS-CoV causes a highly lethal respiratory infection for which no vaccines or antiviral therapeutic options are currently available. Based on continuing exposure from established reservoirs in dromedary camels and bats, transmission of MERS-CoV into humans and future outbreaks are expected. Using structurally defined probes for the MERS-CoV spike glycoprotein (S), the target for neutralizing antibodies, single B cells were sorted from a convalescent human and immunized nonhuman primates (NHPs). MAbs produced from paired immunoglobulin gene sequences were mapped to multiple epitopes within and outside the receptor-binding domain (RBD) and protected against lethal MERS infection in a murine model following passive immunization. Importantly, combining MAbs targeting distinct epitopes prevented viral neutralization escape from RBD-directed MAbs. These data suggest that antibody responses to multiple domains on CoV spike protein may improve immunity and will guide future vaccine and therapeutic development efforts.

scholarly journals In silico analysis of protein/peptide-based inhalers against SARS-CoV-2

2020 ◽  
Vol 15 (9) ◽  
pp. 557-564 ◽  
Author(s):  
Saad Salman ◽  
Fahad Hassan Shah ◽  
Maham Chaudhry ◽  
Muniba Tariq ◽  
Muhammad Yasir Akbar ◽  
...  
Keyword(s):  
Free Energy ◽  
Monoclonal Antibodies ◽  
Molecular Docking ◽  
Binding Free Energy ◽  
In Silico Analysis ◽  
Spike Glycoprotein ◽  
Dornase Alfa ◽  
Alpha 1 Antitrypsin ◽  
Silico Analysis ◽  
Light Chain Antibody

Aim: Peptide/protein-based inhalers are excessively used to treat respiratory disorders. The molecular docking was performed for these inhalers including human neutralizing S230 light chain-antibody (monoclonal antibodies [mAbs]), alpha-1-antitrypsin (AAT), short-palate-lung and nasal-epithelial clone-1-derived peptides (SPLUNC1) and dornase-alfa (DA) against spike glycoprotein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to assess their inhibitory activity. Materials & methods: HawkDock was used to dock these biologics against SARS-CoV-2 spike-glycoprotein. Results: Results showed that DA, AAT and mAb were quite active against spike glycoprotein with a binding free energy of -26.35 and -22.94 kcal/mol. Conclusion: mAB and AAT combined with DA can be used in the treatment of coronavirus disease of 2019 as a potential anti-SARS-CoV-2 agent.

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