Systematic surveillance of SARS-CoV-2 reveals dynamics of variant mutagenesis and transmission in a large urban population.

Publication date: Dec 30, 2024

Highly mutable pathogens generate viral diversity that impacts virulence, transmissibility, treatment, and thwarts acquired immunity. We previously described C19-SPAR-Seq, a high-throughput, next-generation sequencing platform to detect SARS-CoV-2 that we here deployed to systematically profile variant dynamics of SARS-CoV-2 for over 3 years in a large, North American urban environment (Toronto, Canada). Sequencing of the ACE2 receptor binding motif and polybasic furin cleavage site of the Spike gene in over 70,000 patients revealed that population sweeps of canonical variants of concern (VOCs) occurred in repeating wavelets. Furthermore, we found that VOC mutant derivatives and putative quasispecies that targeted functionally important residues and were found in future VOCs arose frequently, but were always extinguished. Systematic screening of functionally relevant domains in pathogens could thus provide a powerful tool for monitoring spread and mutational trajectories, particularly those with zoonotic potential.

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Concepts Keywords
Canada ACE2 protein, human
Viral Angiotensin-Converting Enzyme 2
Virulence Angiotensin-Converting Enzyme 2
Zoonotic COVID-19
High-Throughput Nucleotide Sequencing
Humans
Mutagenesis
Mutation
SARS-CoV-2
Spike Glycoprotein, Coronavirus
Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2
Urban Population

Semantics

Type Source Name
disease IDO virulence
disease IDO site
disease MESH Amelia
disease MESH viral infections
disease MESH COVID 19 pandemic
disease IDO process
drug DRUGBANK 7-Methyl-Gpppa
pathway REACTOME Reproduction
drug DRUGBANK Ranitidine
disease MESH viral load
drug DRUGBANK Amino acids
disease IDO assay
drug DRUGBANK Trestolone
disease IDO history
drug DRUGBANK Etoperidone
disease MESH point mutations
disease IDO quality
disease IDO production
disease IDO replication
drug DRUGBANK Ademetionine
disease IDO infectivity
drug DRUGBANK Succimer
drug DRUGBANK Gold

Original Article

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