Mapping Neutralizing and Immunodominant Sites on the SARS-CoV-2 Spike Receptor-Binding Domain by Structure-Guided High-Resolution Serology

The prompt rollout of the coronavirus disease (COVID-19) messenger RNA (mRNA) vaccine facilitated population immunity, which shall become more dominant than natural infection-induced immunity. At the beginning of the vaccine era, the initial epitope profile in naive individuals will be the first step to build an optimal host defense system towards vaccine-based population immunity. In this study, the high-resolution linear epitope profiles between Pfizer-BioNTech COVID-19 mRNA vaccine recipients and COVID-19 patients were delineated by using microarrays mapped with overlapping peptides of the receptor binding domain (RBD) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. The vaccine-induced antibodies targeting RBD had broader distribution across the RBD than that induced by the natural infection. The relatively lower neutralizing antibody titers observed in vaccine-induced sera could attribute to less efficient epitope selection and maturation of the vaccine-induced humoral immunity compared to the infection-induced. Furthermore, additional mutation panel assays showed that the vaccine-induced rich epitope variety targeting the RBD may aid antibodies to escape rapid viral evolution, which could grant an advantage to the vaccine immunity.

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High-Resolution NMR Structure of the Chemically-Synthesized Melanocortin Receptor Binding Domain AGRP(87−132) of the Agouti-Related Protein†,‡

Biochemistry ◽

10.1021/bi0117192 ◽

2001 ◽

Vol 40 (51) ◽

pp. 15520-15527 ◽

Cited By ~ 55

Author(s):

Joseph C. McNulty ◽

Darren A. Thompson ◽

Kimberly A. Bolin ◽

Jill Wilken ◽

Gregory S. Barsh ◽

...

Keyword(s):

High Resolution ◽

Receptor Binding ◽

Binding Domain ◽

Nmr Structure ◽

Melanocortin Receptor ◽

Receptor Binding Domain ◽

Related Protein ◽

High Resolution Nmr ◽

Agouti Related Protein

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Peer Review #1 of "High resolution crystal structures of the receptor-binding domain of Clostridium botulinum neurotoxin serotypes A and FA (v0.1)"

10.7287/peerj.4552v0.1/reviews/1 ◽

2018 ◽

Keyword(s):

High Resolution ◽

Peer Review ◽

Crystal Structures ◽

Receptor Binding ◽

Clostridium Botulinum ◽

Botulinum Neurotoxin ◽

Binding Domain ◽

Receptor Binding Domain

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Peer Review #3 of "High resolution crystal structures of the receptor-binding domain of Clostridium botulinum neurotoxin serotypes A and FA (v0.1)"

10.7287/peerj.4552v0.1/reviews/3 ◽

2018 ◽

Keyword(s):

High Resolution ◽

Peer Review ◽

Crystal Structures ◽

Receptor Binding ◽

Clostridium Botulinum ◽

Botulinum Neurotoxin ◽

Binding Domain ◽

Receptor Binding Domain

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High-Resolution Linear Epitope Mapping of the Receptor Binding Domain of SARS-CoV-2 Spike Protein in COVID-19 mRNA Vaccine Recipients

Microbiology Spectrum ◽

10.1128/spectrum.00965-21 ◽

2021 ◽

Author(s):

Yuko Nitahara ◽

Yu Nakagama ◽

Natsuko Kaku ◽

Katherine Candray ◽

Yu Michimuko ◽

...

Keyword(s):

High Resolution ◽

Receptor Binding ◽

Epitope Mapping ◽

Binding Domain ◽

Spike Protein ◽

Linear Epitope ◽

Receptor Binding Domain ◽

Population Immunity ◽

Herd Protection ◽

Key Factor

Establishing vaccine-based population immunity has been the key factor in attaining herd protection. Thanks to expedited worldwide research efforts, the potency of mRNA vaccines against the coronavirus disease 2019 (COVID-19) is now incontestable.

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Destabilizing the Structural Integrity of SARS-CoV2 Receptor Proteins by Curcumin Along with Hydroxychloroquine: An Insilco Approach for a Combination Therapy

10.26434/chemrxiv.12090438.v1 ◽

2020 ◽

Cited By ~ 1

Author(s):

Akhileshwar Srivastava ◽

Divya Singh

Keyword(s):

Binding Energy ◽

Combination Therapy ◽

Receptor Binding ◽

Structural Integrity ◽

Binding Domain ◽

Receptor Binding Domain ◽

Receptor Proteins ◽

Main Protease ◽

The Stability ◽

Therapeutic Activities

Presently, an emerging disease (COVID-19) has been spreading across the world due to coronavirus (SARS-CoV2). For treatment of SARS-CoV2 infection, currently hydroxychloroquine has been suggested by researchers, but it has not been found enough effective against this virus. The present study based on in silico approaches was designed to enhance the therapeutic activities of hydroxychloroquine by using curcumin as an adjunct drug against SARS-CoV2 receptor proteins: main-protease and S1 receptor binding domain (RBD). The webserver (ANCHOR) showed the higher protein stability for both receptors with disordered score (<0.5). The molecular docking analysis revealed that the binding energy (-24.58 kcal/mol) of hydroxychloroquine was higher than curcumin (-20.47 kcal/mol) for receptor main-protease, whereas binding energy of curcumin (<a>-38.84</a> kcal/mol) had greater than hydroxychloroquine<a> (-35.87</a> kcal/mol) in case of S1 receptor binding domain. Therefore, this study suggested that the curcumin could be used as combination therapy along with hydroxychloroquine for disrupting the stability of SARS-CoV2 receptor proteins

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Amoxicillin Trihydrate-Clavulanate Potassium As Potential Inhibitor of 2019 Novel Coronavirus Main Protease with Strong Receptor-Binding Domain (RBD), Molecular Docking and SAR Study

SSRN Electronic Journal ◽

10.2139/ssrn.3580230 ◽

2020 ◽

Author(s):

Khedidja benarous ◽

Talia Serseg ◽

Mohamed Yousfi

Keyword(s):

Molecular Docking ◽

Receptor Binding ◽

Binding Domain ◽

Receptor Binding Domain ◽

Potential Inhibitor ◽

Main Protease ◽

Amoxicillin Trihydrate ◽

Novel Coronavirus ◽

Sar Study

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Amoxicillin and Clavulanate as Potential Multiple Effect Inhibitors of 2019 Novel Coronavirus Main Protease and RNA-Dependent RNA Polymerase with Strong Receptor-Binding Domain (RBD), Molecular Docking and SAR Study

SSRN Electronic Journal ◽

10.2139/ssrn.3618303 ◽

2020 ◽

Author(s):

Khedidja benarous ◽

Talia Serseg ◽

Mohamed Yousfi

Keyword(s):

Molecular Docking ◽

Rna Polymerase ◽

Receptor Binding ◽

Binding Domain ◽

Receptor Binding Domain ◽

Rna Dependent Rna Polymerase ◽

Multiple Effect ◽

Main Protease ◽

Novel Coronavirus ◽

Sar Study

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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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