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Sequence analysis of SARS-CoV-2 genome reveals features important for vaccine design

Jacob Kames, David D. Holcomb, View ORCID ProfileOfer Kimchi, Michael DiCuccio, Nobuko Hamasaki-Katagiri, Tony Wang, Anton A. Komar, Aikaterini Alexaki, View ORCID ProfileChava Kimchi-Sarfaty
doi: https://doi.org/10.1101/2020.03.30.016832
Jacob Kames
1Center for Biologics Evaluation and Research, Office of Tissues and Advanced Therapies, Division of Plasma Protein Therapeutics, Food and Drug Administration, Silver Spring, MD, USA
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David D. Holcomb
1Center for Biologics Evaluation and Research, Office of Tissues and Advanced Therapies, Division of Plasma Protein Therapeutics, Food and Drug Administration, Silver Spring, MD, USA
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Ofer Kimchi
2Harvard University School of Engineering and Applied Sciences
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Michael DiCuccio
3National Center of Biotechnology Information, National Institutes of Health, Bethesda, MD, USA
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Nobuko Hamasaki-Katagiri
1Center for Biologics Evaluation and Research, Office of Tissues and Advanced Therapies, Division of Plasma Protein Therapeutics, Food and Drug Administration, Silver Spring, MD, USA
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Tony Wang
4Center for Biologics Evaluation and Research, Office of Vaccines Research and Review, Division of Viral Products, Food and Drug Administration, Silver Spring, MD, USA
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Anton A. Komar
5Center for Gene Regulation in Health and Disease, Cleveland State University, Cleveland, OH, USA
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Aikaterini Alexaki
1Center for Biologics Evaluation and Research, Office of Tissues and Advanced Therapies, Division of Plasma Protein Therapeutics, Food and Drug Administration, Silver Spring, MD, USA
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  • For correspondence: Chava.kimchi-sarfaty@fda.hhs.gov Aikaterini.alexaki@fda.hhs.gov
Chava Kimchi-Sarfaty
1Center for Biologics Evaluation and Research, Office of Tissues and Advanced Therapies, Division of Plasma Protein Therapeutics, Food and Drug Administration, Silver Spring, MD, USA
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  • ORCID record for Chava Kimchi-Sarfaty
  • For correspondence: Chava.kimchi-sarfaty@fda.hhs.gov Aikaterini.alexaki@fda.hhs.gov
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Abstract

As the SARS-CoV-2 pandemic is rapidly progressing, the need for the development of an effective vaccine is critical. A promising approach for vaccine development is to generate, through codon pair deoptimization, an attenuated virus. This approach carries the advantage that it only requires limited knowledge specific to the virus in question, other than its genome sequence. Therefore, it is well suited for emerging viruses for which we may not have extensive data. We performed comprehensive in silico analyses of several features of SARS-CoV-2 genomic sequence (e.g., codon usage, codon pair usage, dinucleotide/junction dinucleotide usage, RNA structure around the frameshift region) in comparison with other members of the coronaviridae family of viruses, the overall human genome, and the transcriptome of specific human tissues such as lung, which are primarily targeted by the virus. Our analysis identified the spike (S) and nucleocapsid (N) proteins as promising targets for deoptimization and suggests a roadmap for SARS-CoV-2 vaccine development, which can be generalizable to other viruses.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted March 31, 2020.
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Sequence analysis of SARS-CoV-2 genome reveals features important for vaccine design
Jacob Kames, David D. Holcomb, Ofer Kimchi, Michael DiCuccio, Nobuko Hamasaki-Katagiri, Tony Wang, Anton A. Komar, Aikaterini Alexaki, Chava Kimchi-Sarfaty
bioRxiv 2020.03.30.016832; doi: https://doi.org/10.1101/2020.03.30.016832
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Sequence analysis of SARS-CoV-2 genome reveals features important for vaccine design
Jacob Kames, David D. Holcomb, Ofer Kimchi, Michael DiCuccio, Nobuko Hamasaki-Katagiri, Tony Wang, Anton A. Komar, Aikaterini Alexaki, Chava Kimchi-Sarfaty
bioRxiv 2020.03.30.016832; doi: https://doi.org/10.1101/2020.03.30.016832

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