SARS-CoV-2 Genotyping Highlights the Challenges in Spike Protein Drift Independent of Other Essential Proteins

Prokop, Jeremy W.; Alberta, Sheryl; Witteveen-Lane, Martin; Pell, Samantha; Farag, Hosam A.; Bhargava, Disha; Vaughan, Robert M.; Frisch, Austin; Bauss, Jacob; Bhatti, Humza; Arora, Sanjana; Subrahmanya, Charitha; Pearson, David; Goodyke, Austin; Westgate, Mason; Cook, Taylor W.; Mitchell, Jackson T.; Zieba, Jacob; Sims, Matthew D.; Underwood, Adam; Hassouna, Habiba; Rajasekaran, Surender; Tamae Kakazu, Maximiliano A.; Chesla, Dave; Olivero, Rosemary; Caulfield, Adam J.

doi:10.3390/microorganisms12091863

Open AccessArticle

SARS-CoV-2 Genotyping Highlights the Challenges in Spike Protein Drift Independent of Other Essential Proteins

by

Jeremy W. Prokop

^1,2,*,

Sheryl Alberta

³,

Martin Witteveen-Lane

¹,

Samantha Pell

³,

Hosam A. Farag

¹,

Disha Bhargava

²,

Robert M. Vaughan

²

,

Austin Frisch

²,

Jacob Bauss

²,

Humza Bhatti

²

,

Sanjana Arora

¹,

Charitha Subrahmanya

¹,

David Pearson

¹,

Austin Goodyke

¹

,

Mason Westgate

¹,

Taylor W. Cook

²,

Jackson T. Mitchell

²,

Jacob Zieba

⁴,

Matthew D. Sims

^5,6,

Adam Underwood

⁷

,

Habiba Hassouna

⁸,

Surender Rajasekaran

^1,2,

Maximiliano A. Tamae Kakazu

^2,9

,

Dave Chesla

^1,2,

Rosemary Olivero

^2,10

and

Adam J. Caulfield

^11,* Show full author list Hide full author list

¹

Office of Research, Corewell Health, Grand Rapids, MI 49503, USA

²

College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA

³

Advanced Technology Lab, Corewell Health, Grand Rapids, MI 49503, USA

⁴

Genetics and Genome Sciences Program, BioMolecular Science, Michigan State University, East Lansing, MI 48824, USA

⁵

Section of Infectious Diseases, Corewell Health, Royal Oak, MI 48073, USA

⁶

Department of Internal Medicine, Oakland University William Beaumont School of Medicine, Auburn Hills, MI 48309, USA

⁷

Division of Mathematics and Science, Walsh University, North Canton, OH 44720, USA

⁸

Adult Infectious Disease, Corewell Health, Grand Rapids, MI 49503, USA

⁹

Division of Pulmonary and Critical Care Medicine, Corewell Health, Grand Rapids, MI 49503, USA

¹⁰

Pediatric Infectious Disease, Helen DeVos Children’s Hospital, Corewell Health, Grand Rapids, MI 49503, USA

¹¹

Microbiology Lab, Corewell Health, Grand Rapids, MI 49503, USA

Show full affiliation list

Hide full affiliation list

^*

Authors to whom correspondence should be addressed.

Microorganisms 2024, 12(9), 1863; https://doi.org/10.3390/microorganisms12091863

Submission received: 1 August 2024 / Revised: 22 August 2024 / Accepted: 27 August 2024 / Published: 9 September 2024

(This article belongs to the Special Issue New Knowledge in the Study of Coronaviruses: Towards One Health and Whole Genome Sequencing Approaches, 2nd Edition)

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Abstract

As of 2024, SARS-CoV-2 continues to propagate and drift as an endemic virus, impacting healthcare for years. The largest sequencing initiative for any species was initiated to combat the virus, tracking changes over time at a full virus base-pair resolution. The SARS-CoV-2 sequencing represents a unique opportunity to understand selective pressures and viral evolution but requires cross-disciplinary approaches from epidemiology to functional protein biology. Within this work, we integrate a two-year genotyping window with structural biology to explore the selective pressures of SARS-CoV-2 on protein insights. Although genotype and the Spike (Surface Glycoprotein) protein continue to drift, most SARS-CoV-2 proteins have had few amino acid alterations. Within Spike, the high drift rate of amino acids involved in antibody evasion also corresponds to changes within the ACE2 binding pocket that have undergone multiple changes that maintain functional binding. The genotyping suggests selective pressure for receptor specificity that could also confer changes in viral risk. Mapping of amino acid changes to the structures of the SARS-CoV-2 co-transcriptional complex (nsp7-nsp14), nsp3 (papain-like protease), and nsp5 (cysteine protease) proteins suggest they remain critical factors for drug development that will be sustainable, unlike those strategies targeting Spike.

Keywords: SARS-CoV-2; COVID-19; viral genome; drift; Spike; nonstructural protein; papain-like protease; cysteine protease

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MDPI and ACS Style

Prokop, J.W.; Alberta, S.; Witteveen-Lane, M.; Pell, S.; Farag, H.A.; Bhargava, D.; Vaughan, R.M.; Frisch, A.; Bauss, J.; Bhatti, H.; et al. SARS-CoV-2 Genotyping Highlights the Challenges in Spike Protein Drift Independent of Other Essential Proteins. Microorganisms 2024, 12, 1863. https://doi.org/10.3390/microorganisms12091863

AMA Style

Prokop JW, Alberta S, Witteveen-Lane M, Pell S, Farag HA, Bhargava D, Vaughan RM, Frisch A, Bauss J, Bhatti H, et al. SARS-CoV-2 Genotyping Highlights the Challenges in Spike Protein Drift Independent of Other Essential Proteins. Microorganisms. 2024; 12(9):1863. https://doi.org/10.3390/microorganisms12091863

Chicago/Turabian Style

Prokop, Jeremy W., Sheryl Alberta, Martin Witteveen-Lane, Samantha Pell, Hosam A. Farag, Disha Bhargava, Robert M. Vaughan, Austin Frisch, Jacob Bauss, Humza Bhatti, and et al. 2024. "SARS-CoV-2 Genotyping Highlights the Challenges in Spike Protein Drift Independent of Other Essential Proteins" Microorganisms 12, no. 9: 1863. https://doi.org/10.3390/microorganisms12091863

APA Style

Prokop, J. W., Alberta, S., Witteveen-Lane, M., Pell, S., Farag, H. A., Bhargava, D., Vaughan, R. M., Frisch, A., Bauss, J., Bhatti, H., Arora, S., Subrahmanya, C., Pearson, D., Goodyke, A., Westgate, M., Cook, T. W., Mitchell, J. T., Zieba, J., Sims, M. D., ... Caulfield, A. J. (2024). SARS-CoV-2 Genotyping Highlights the Challenges in Spike Protein Drift Independent of Other Essential Proteins. Microorganisms, 12(9), 1863. https://doi.org/10.3390/microorganisms12091863

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SARS-CoV-2 Genotyping Highlights the Challenges in Spike Protein Drift Independent of Other Essential Proteins

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