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

7 Scopus citations

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)
Journal	Molecular biology and evolution
Volume	39
Issue number	5
DOIs	https://doi.org/10.1093/molbev/msac091
State	Published - May 3 2022
Externally published	Yes

Bibliographical note

KAUST Repository Item: Exported on 2022-06-01
Acknowledgements: We thank Dr Milka Kostic (Life Science Editors) for professional editorial services. We thank Dr Intikhab S. Alam (King Abdullah University of Science and Technology) for his assistance with querying the COVID-19 virusMutation Tracker. This work was supported in part by core services from Rutgers Cancer Institute of New Jersey (NCI Cancer Center Support Grant number P30CA072720); by the RCSB Protein Data Bank, which is jointly funded by the National Science Foundation (NSF) (grant number DBI-1832184), the US Department of Energy (grant number DOE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health (NIH) (grant number R01GM133198); by NSF grants (grant numbers CHE-1614101 and PHY-1522550 to J.N.O. and grant number MCB-1915843 to P.C.W.); and by awards from the Levy-Longenbaugh Donor-Advised Fund (to R.P. and W.A.), and the Welch Foundation (grant number C-1792 to J.N.O.). The work at the Center for Theoretical Biological Physics was also supported by the NSF (grant number PHY-2019745). J.N.O. is a Cancer Prevention Research in Texas Scholar in Cancer Research. The work at Houston Methodist Research Institute was partly supported by the Cockrell Foundation (to P.D.) and the NIH (grant number 1R01CA253865 to Z.W. and V.C.; grant number 1R01CA222007 to Z.W. and V.C.; grant number 1R01CA226537 to Z.W., V.C., R.P., and W.A.). We are grateful for the computational resources and support provided by the AMD COVID-19 High Performance Computing (HPC) Fund program, the Northeastern University Discovery cluster, and the Northeastern University Research Computing staff.
This publication acknowledges KAUST support, but has no KAUST affiliated authors.

ASJC Scopus subject areas

Ecology, Evolution, Behavior and Systematics
Genetics
Molecular Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1093/molbev/msac091

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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). https://doi.org/10.1093/molbev/msac091

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title = "Genetic and Structural Analysis of SARS-CoV-2 Spike Protein for Universal Epitope Selection",

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.",

author = "Christopher Markosian and Staquicini, {Daniela I} and Prashant Dogra and Esteban Dodero-Rojas and Lubin, {Joseph H} and Tang, {Fenny H F} and Smith, {Tracey L} and Contessoto, {Vin{\'i}cius G} and Libutti, {Steven K} and Zhihui Wang and Vittorio Cristini and Khare, {Sagar D} and Whitford, {Paul C} and Burley, {Stephen K} and Onuchic, {Jos{\'e} N} and Renata Pasqualini and Wadih Arap",

note = "KAUST Repository Item: Exported on 2022-06-01 Acknowledgements: We thank Dr Milka Kostic (Life Science Editors) for professional editorial services. We thank Dr Intikhab S. Alam (King Abdullah University of Science and Technology) for his assistance with querying the COVID-19 virusMutation Tracker. This work was supported in part by core services from Rutgers Cancer Institute of New Jersey (NCI Cancer Center Support Grant number P30CA072720); by the RCSB Protein Data Bank, which is jointly funded by the National Science Foundation (NSF) (grant number DBI-1832184), the US Department of Energy (grant number DOE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health (NIH) (grant number R01GM133198); by NSF grants (grant numbers CHE-1614101 and PHY-1522550 to J.N.O. and grant number MCB-1915843 to P.C.W.); and by awards from the Levy-Longenbaugh Donor-Advised Fund (to R.P. and W.A.), and the Welch Foundation (grant number C-1792 to J.N.O.). The work at the Center for Theoretical Biological Physics was also supported by the NSF (grant number PHY-2019745). J.N.O. is a Cancer Prevention Research in Texas Scholar in Cancer Research. The work at Houston Methodist Research Institute was partly supported by the Cockrell Foundation (to P.D.) and the NIH (grant number 1R01CA253865 to Z.W. and V.C.; grant number 1R01CA222007 to Z.W. and V.C.; grant number 1R01CA226537 to Z.W., V.C., R.P., and W.A.). We are grateful for the computational resources and support provided by the AMD COVID-19 High Performance Computing (HPC) Fund program, the Northeastern University Discovery cluster, and the Northeastern University Research Computing staff. This publication acknowledges KAUST support, but has no KAUST affiliated authors.",

year = "2022",

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doi = "10.1093/molbev/msac091",

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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. https://doi.org/10.1093/molbev/msac091

TY - JOUR

T1 - Genetic and Structural Analysis of SARS-CoV-2 Spike Protein for Universal Epitope Selection

AU - Markosian, Christopher

AU - Staquicini, Daniela I

AU - Dogra, Prashant

AU - Dodero-Rojas, Esteban

AU - Lubin, Joseph H

AU - Tang, Fenny H F

AU - Smith, Tracey L

AU - Contessoto, Vinícius G

AU - Libutti, Steven K

AU - Wang, Zhihui

AU - Cristini, Vittorio

AU - Khare, Sagar D

AU - Whitford, Paul C

AU - Burley, Stephen K

AU - Onuchic, José N

AU - Pasqualini, Renata

AU - Arap, Wadih

N1 - KAUST Repository Item: Exported on 2022-06-01 Acknowledgements: We thank Dr Milka Kostic (Life Science Editors) for professional editorial services. We thank Dr Intikhab S. Alam (King Abdullah University of Science and Technology) for his assistance with querying the COVID-19 virusMutation Tracker. This work was supported in part by core services from Rutgers Cancer Institute of New Jersey (NCI Cancer Center Support Grant number P30CA072720); by the RCSB Protein Data Bank, which is jointly funded by the National Science Foundation (NSF) (grant number DBI-1832184), the US Department of Energy (grant number DOE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health (NIH) (grant number R01GM133198); by NSF grants (grant numbers CHE-1614101 and PHY-1522550 to J.N.O. and grant number MCB-1915843 to P.C.W.); and by awards from the Levy-Longenbaugh Donor-Advised Fund (to R.P. and W.A.), and the Welch Foundation (grant number C-1792 to J.N.O.). The work at the Center for Theoretical Biological Physics was also supported by the NSF (grant number PHY-2019745). J.N.O. is a Cancer Prevention Research in Texas Scholar in Cancer Research. The work at Houston Methodist Research Institute was partly supported by the Cockrell Foundation (to P.D.) and the NIH (grant number 1R01CA253865 to Z.W. and V.C.; grant number 1R01CA222007 to Z.W. and V.C.; grant number 1R01CA226537 to Z.W., V.C., R.P., and W.A.). We are grateful for the computational resources and support provided by the AMD COVID-19 High Performance Computing (HPC) Fund program, the Northeastern University Discovery cluster, and the Northeastern University Research Computing staff. This publication acknowledges KAUST support, but has no KAUST affiliated authors.

PY - 2022/5/3

Y1 - 2022/5/3

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.

AB - 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.

UR - http://hdl.handle.net/10754/678356

UR - https://academic.oup.com/mbe/article/doi/10.1093/molbev/msac091/6577179

U2 - 10.1093/molbev/msac091

DO - 10.1093/molbev/msac091

M3 - Article

C2 - 35511693

SN - 0737-4038

VL - 39

JO - Molecular biology and evolution

JF - Molecular biology and evolution

IS - 5

ER -

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

Abstract

Bibliographical note

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UN SDGs

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