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

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 un...

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Published in:	Microorganisms (Basel) Vol. 12; no. 9; p. 1863
Main Authors:	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
Format:	Journal Article
Language:	English
Published:	Switzerland MDPI AG 09-09-2024 MDPI
Subjects:	ACE2 Amino acid sequence Amino acids Angiotensin-converting enzyme 2 Annotations Binding Biology COVID-19 Cysteine proteinase Drift Drift rate Drug development Endemic species Epidemiology Firing rate Genomes Genomics Genotype & phenotype Genotypes Genotyping Glycoproteins Health aspects Hospital systems nonstructural protein Pandemics Papain Peptide mapping Phylogenetics Protease Proteases Proteins SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 Software Spike Spike protein Sustainable development Viral diseases viral genome Viruses Michigan United States > US Germany COVID-19 Spike cysteine protease SARS-CoV-2 viral genome papain-like protease drift nonstructural protein
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2076-2607 2076-2607
DOI:	10.3390/microorganisms12091863