Genetic and Structural Analysis of SARS-CoV-2 Spike Protein for Universal Epitope Selection

Christopher Markosian; Daniela I. Staquicini; Prashant Dogra; Esteban Dodero-Rojas; Joseph H. Lubin; Fenny H.F. Tang; Tracey L. Smith; Vinícius G. Contessoto; Steven K. Libutti; Zhihui Wang; Vittorio Cristini; Sagar D. Khare; Paul C. Whitford; Stephen K. Burley; José N. Onuchic; Renata Pasqualini; Wadih Arap

doi:10.1093/molbev/msac091

Genetic and Structural Analysis of SARS-CoV-2 Spike Protein for Universal Epitope Selection

Christopher Markosian, Daniela I. Staquicini, Prashant Dogra, Esteban Dodero-Rojas, Joseph H. Lubin, Fenny H.F. Tang, Tracey L. Smith, Vinícius G. Contessoto, Steven K. Libutti, Zhihui Wang, Vittorio Cristini, Sagar D. Khare, Paul C. Whitford, Stephen K. Burley, José N. Onuchic, Renata Pasqualini, Wadih Arap

Research output: Contribution to journal › Article › peer-review

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Abstract

Evaluation of immunogenic epitopes for universal vaccine development in the face of ongoing SARS-CoV-2 evolution remains a challenge. Herein, we investigate the genetic and structural conservation of an immunogenically relevant epitope (C662-C671) of spike (S) protein across SARS-CoV-2 variants to determine its potential utility as a broad-spectrum vaccine candidate against coronavirus diseases. Comparative sequence analysis, structural assessment, and molecular dynamics simulations of C662-C671 epitope were performed. Mathematical tools were employed to determine its mutational cost. We found that the amino acid sequence of C662-C671 epitope is entirely conserved across the observed major variants of SARS-CoV-2 in addition to SARS-CoV. Its conformation and accessibility are predicted to be conserved, even in the highly mutated Omicron variant. Costly mutational rate in the context of energy expenditure in genome replication and translation can explain this strict conservation. These observations may herald an approach to developing vaccine candidates for universal protection against emergent variants of coronavirus.

Original language	English (US)
Article number	msac091
Journal	Molecular Biology and Evolution
Volume	39
Issue number	5
DOIs	https://doi.org/10.1093/molbev/msac091
State	Published - May 1 2022

Keywords

COVID-19
epitope
variants
SARS-CoV-2/genetics
Humans
Spike Glycoprotein, Coronavirus/chemistry
Vaccines
Epitopes, T-Lymphocyte/chemistry

ASJC Scopus subject areas

Genetics
Ecology, Evolution, Behavior and Systematics
Molecular Biology

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Markosian, C., Staquicini, D. I., Dogra, P., Dodero-Rojas, E., Lubin, J. H., Tang, F. H. F., Smith, T. L., Contessoto, V. G., Libutti, S. K., Wang, Z., Cristini, V., Khare, S. D., Whitford, P. C., Burley, S. K., Onuchic, J. N., Pasqualini, R., & Arap, W. (2022). Genetic and Structural Analysis of SARS-CoV-2 Spike Protein for Universal Epitope Selection. Molecular Biology and Evolution, 39(5), Article msac091. https://doi.org/10.1093/molbev/msac091

Markosian, C, Staquicini, DI, Dogra, P, Dodero-Rojas, E, Lubin, JH, Tang, FHF, Smith, TL, Contessoto, VG, Libutti, SK, Wang, Z , Cristini, V, Khare, SD, Whitford, PC, Burley, SK, Onuchic, JN, Pasqualini, R & Arap, W 2022, 'Genetic and Structural Analysis of SARS-CoV-2 Spike Protein for Universal Epitope Selection', Molecular Biology and Evolution, vol. 39, no. 5, msac091. https://doi.org/10.1093/molbev/msac091

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abstract = "Evaluation of immunogenic epitopes for universal vaccine development in the face of ongoing SARS-CoV-2 evolution remains a challenge. Herein, we investigate the genetic and structural conservation of an immunogenically relevant epitope (C662-C671) of spike (S) protein across SARS-CoV-2 variants to determine its potential utility as a broad-spectrum vaccine candidate against coronavirus diseases. Comparative sequence analysis, structural assessment, and molecular dynamics simulations of C662-C671 epitope were performed. Mathematical tools were employed to determine its mutational cost. We found that the amino acid sequence of C662-C671 epitope is entirely conserved across the observed major variants of SARS-CoV-2 in addition to SARS-CoV. Its conformation and accessibility are predicted to be conserved, even in the highly mutated Omicron variant. Costly mutational rate in the context of energy expenditure in genome replication and translation can explain this strict conservation. These observations may herald an approach to developing vaccine candidates for universal protection against emergent variants of coronavirus.",

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N2 - Evaluation of immunogenic epitopes for universal vaccine development in the face of ongoing SARS-CoV-2 evolution remains a challenge. Herein, we investigate the genetic and structural conservation of an immunogenically relevant epitope (C662-C671) of spike (S) protein across SARS-CoV-2 variants to determine its potential utility as a broad-spectrum vaccine candidate against coronavirus diseases. Comparative sequence analysis, structural assessment, and molecular dynamics simulations of C662-C671 epitope were performed. Mathematical tools were employed to determine its mutational cost. We found that the amino acid sequence of C662-C671 epitope is entirely conserved across the observed major variants of SARS-CoV-2 in addition to SARS-CoV. Its conformation and accessibility are predicted to be conserved, even in the highly mutated Omicron variant. Costly mutational rate in the context of energy expenditure in genome replication and translation can explain this strict conservation. These observations may herald an approach to developing vaccine candidates for universal protection against emergent variants of coronavirus.

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Genetic and Structural Analysis of SARS-CoV-2 Spike Protein for Universal Epitope Selection

Abstract

Keywords

ASJC Scopus subject areas

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