Comparative computational analysis of SARS-CoV-2 nucleocapsid protein epitopes in taxonomically related coronaviruses

Tilocca, Bruno; Soggiu, Alessio; Sanguinetti, Maurizio; Musella, Vincenzo; Britti, Domenico; Bonizzi, L.; Urbani, Andrea; Roncada, Paola

doi:10.1016/j.micinf.2020.04.002

Cited by 130 publications

(135 citation statements)

References 18 publications

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“…[ Ahmed et al 2020]. It is worth noting that these epitopes were also considered in another study aiming to provide a molecular structural rationale of the major nucleocapsid protein epitopes for a potential role in conferring protection from SARS-CoV-2 infection [Tilocca et al 2020]. We herein focused on the SARS-CoV-2 N and S proteins because both these two proteins are the main targets of vaccines and antiviral drugs due to their dominant and long-lasting immune response previously reported against SARS-CoV [Ahmed et al 2020.We aligned the homologous protein sequences in the seven human coronaviruses and used the resulting alignment to calculate a conservation profile by using the software Rate4site [Pupko et al 2002] (see Materials and Methods).…”

Section: Identification Of Conserved Epitopes In Spike and Nucleocapsmentioning

confidence: 99%

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Identification of conserved epitopes in SARS-CoV-2 spike and nucleocapsid protein

Forcelloni

Benedetti

Dilucca

et al. 2020

Preprint

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which first occurred in Wuhan (China) in December 2019, is a novel virus that causes a severe acute respiratory disease. The virus spike glycoproteins and nucleocapsid proteins are the main targets for the development of vaccines and antiviral drugs, to control the disease spread. We herein study the structural order-disorder propensity and the rates of evolution of these two proteins to characterize their B cell and T cell epitopes, previously suggested to contribute to immune response caused by SARS-CoV-2 infections.We first analyzed the rates of evolution along the sequences of spike and nucleocapsid proteins in relation to the spatial locations of their epitopes. For this purpose, we compared orthologs from seven human coronaviruses: SARS-CoV-2, SARS-CoV, MERS-CoV, HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1. We then focus on the local, structural order-disorder propensities of the protein regions where the SARS-CoV-2 epitopes are located. We show that the vast majority of nucleocapsid protein epitopes overlap the RNA-binding and dimerization domains and some of them are characterized by low rates of evolutions. Similarly, spike protein epitopes are preferentially located in regions that are predicted to be ordered and well-conserved, in correspondence of the heptad repeats 1 and 2. Interestingly, both the receptor-binding motif to ACE2 and the fusion peptide of spike protein are characterized by high rates of evolution, probably to overcome host immunity. In conclusion, our results provide evidence for conserved epitopes that may help to develop long-lasting, broad-spectrum SARS-CoV-2 vaccines.

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Section: Identification Of Conserved Epitopes In Spike and Nucleocapsmentioning

confidence: 99%

“…The N protein is of potential interest for vaccine development as it is highly immunogenic and its amino acid sequence is highly conserved. This protein contains two structural domains: the N-terminal domain, that acts as a putative RNA binding domain, and a C-terminal domain, which acts as a dimerization domain [Tilocca et al 2020].…”

Section: Introductionmentioning

confidence: 99%

Identification of conserved epitopes in SARS-CoV-2 spike and nucleocapsid protein

Forcelloni

Benedetti

Dilucca

et al. 2020

Preprint

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“…Another recent study that identified epitopes in the SARS-CoV-2 N protein found the N protein in pangolin CoV failed to align with two of those epitope sequences. 44 From this, the authors claim separations exist between functional adaptation and molecular evolution. There are variations between NTDs in SARS-CoV-2 and Pangolin-CoV MP789; despite their N proteins having a close evolutionary history.…”

Section: Resultsmentioning

confidence: 99%

“…Given the N protein is immunogenetic, knowing the amino acid and structural differences can be useful for developing antigens in serological detection, antiviral medications, and vaccine candidates. 11,44 In regard to the flexible coils in Pangolin-CoV MP789 and Bat-CoV RaTG13, these features might also be inherent to their respective NTDs. Based on the data used to verify homology models, it seems these features are not errors as each model presented with ideal values for energy and stereochemical quality.…”

Section: Resultsmentioning

confidence: 99%

Using nucleocapsid proteins to investigate the relationship between SARS-CoV-2 and closely related bat and pangolin coronaviruses

Schuster

2020

Preprint

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AbstractAn initial outbreak of coronavirus disease 2019 (COVID-19) in China has resulted in a massive global pandemic causing well over 10,000,000 cases and 500,000 deaths worldwide. The virus responsible, SARS-CoV-2, has been found to possess a very close association with Bat-CoV RaTG13 and Pangolin-CoV MP789. The nucleocapsid protein can serve as a decent model for determining phylogenetic, evolutionary, and structural relationships between coronaviruses. Therefore, this study uses the nucleocapsid gene and protein to further investigate the relationship between SARS-CoV-2 and closely related bat and pangolin coronaviruses. Sequence and phylogenetic analyses have revealed the nucleocapsid gene and protein in SARS-CoV-2 are both closely related to those found in Bat-CoV RaTG13 and Pangolin-CoV MP789. Evidence of recombination was detected within the N gene, along with the presence of a double amino acid insertion found in the N-terminal region. Homology modeling for the N-Terminal Domain revealed similar structures but distinct electrostatic surfaces and topological variations in the β-hairpin that likely reflect specific adaptive functions. In respect to SARS-CoV-2, two amino acids (37S and 267A) were found to exist only in its N protein, along with an extended β-hairpin in the N-Terminal Domain. Collectively, this study strengthens the relationship among SARS-CoV-2, Bat-CoV RaTG13, and Pangolin-CoV MP789, providing additional insights into the structure and adaptive nature of the nucleocapsid protein found in these coronaviruses. Furthermore, this data will help enhance our understanding of the complete history behind SARS-CoV-2 and help assist in antiviral and vaccine development.

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“…Nucleocapsid protein, with a mass of 50 kDa, is the most abundant macromolecule in coronaviruses and is highly immunogenic [ 52 ]. The comparison of the whole amino acid sequence of chosen N proteins revealed 87.86% similarity between SARS-CoV-2 and pangolin CoV, 90% similarity to SARS-CoV, and 99% similarity to bat CoV [ 52 ]. The nucleocapsid protein of SARS-CoV has the capacity to neutralize the immune response of the host.…”

Section: Differences and Similarities Between Sars-cov And Sars-comentioning

confidence: 99%

Mass Spectrometry and Structural Biology Techniques in the Studies on the Coronavirus-Receptor Interaction

Witkowska

2020

Molecules

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Mass spectrometry and some other biophysical methods, have made substantial contributions to the studies on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and human proteins interactions. The most interesting feature of SARS-CoV-2 seems to be the structure of its spike (S) protein and its interaction with the human cell receptor. Mass spectrometry of spike S protein revealed how the glycoforms are distributed across the S protein surface. X-ray crystallography and cryo-electron microscopy made huge impact on the studies on the S protein and ACE2 receptor protein interaction, by elucidating the three-dimensional structures of these proteins and their conformational changes. The findings of the most recent studies in the scope of SARS-CoV-2-Human protein-protein interactions are described here.

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Comparative computational analysis of SARS-CoV-2 nucleocapsid protein epitopes in taxonomically related coronaviruses

Cited by 130 publications

References 18 publications

Identification of conserved epitopes in SARS-CoV-2 spike and nucleocapsid protein

Identification of conserved epitopes in SARS-CoV-2 spike and nucleocapsid protein

Using nucleocapsid proteins to investigate the relationship between SARS-CoV-2 and closely related bat and pangolin coronaviruses

Mass Spectrometry and Structural Biology Techniques in the Studies on the Coronavirus-Receptor Interaction

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