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 journalArticlepeer-review

1 Scopus citations


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 languageEnglish (US)
JournalMolecular biology and evolution
Issue number5
StatePublished - May 3 2022
Externally publishedYes

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


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