ArticleGenome biology2023
The P323L substitution in the SARS-CoV-2 polymerase (NSP12) confers a selective advantage during infection.
Article in Genome biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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22 citing papers in PubMed, 41 citations in OpenAlex.
- A Cross-Sectional Study Shows Emergence of the Delta, 19B, 20A, 20B, 19A, and Omicron Variants of SARS-CoV-2 in Burkina Faso: A Conundrum Within a Conundrum.Health science reports · 2026Article
- The Enigmatic Conserved Q134-F135-N137 Triad in SARS-CoV-2 Spike Protein: A Conformational Transducer?Biomolecules · 2026Review
- Molecular characterization and evolutionary dynamics of a recombinant PDCoV strain in a swine diarrhea epidemic with SADS-CoV co-infection.Frontiers in veterinary science · 2026Article
- Development of the coronavirus reverse genetic system: Core technology for pathogenesis mechanisms research and vaccine/drug development.Virulence · 2025Review
- Development of RNA Aptamers That Inhibit the RNA-Dependent RNA Polymerase Activity of SARS-CoV-2 Strains In Vitro.International journal of molecular sciences · 2025Article
- The C-terminal Domain of SARS-CoV-2 nsp8 is a Molten Globule in the Absence of Binding Partners.Journal of molecular biology · 2025Article
- Spatial Transcriptomics and Single Cell-RNASeq Reveals Cellular Heterogeneity of SARS-CoV-2 in Lung Tissues and Global Mutational Patterns in COVID-19 Patients.Journal of medical virology · 2025Article
- Article
- A post-assembly conformational change makes the SARS-CoV-2 polymerase elongation-competent.Nucleic acids research · 2025Article
- The effect of molnupiravir and nirmatrelvir on SARS-CoV-2 genome diversity in severe models of COVID-19.Microbiology spectrum · 2025Article
- A Novel Toolkit of SARS-CoV-2 Sub-Genomic Replicons for Efficient Antiviral Screening.Viruses · 2025Article
- A comprehensive review of current insights into the virulence factors of SARS-CoV-2.Journal of virology · 2025Review
- Using minor variant genomes and machine learning to study the genome biology of SARS-CoV-2 over time.Nucleic acids research · 2025Article
- Biochemical characterization of naturally occurring mutations in SARS-CoV-2 RNA-dependent RNA polymerase.Protein science : a publication of the Protein Society · 2024Article
- Comparative Atlas of SARS-CoV-2 Substitution Mutations: A Focus on Iranian Strains Amidst Global Trends.Viruses · 2024Article
- SARS-CoV-2 population dynamics in immunocompetent individuals in a closed transmission chain shows genomic diversity over the course of infection.Genome medicine · 2024Article
- COVID-19 cluster surveillance using exposure data collected from routine contact tracing: The genomic validation of a novel informatics-based approach to outbreak detection in England.PLOS digital health · 2024Article
- Novel sofosbuvir derivatives against SARS-CoV-2 RNA-dependent RNA polymerase: an in silico perspective.Scientific reports · 2023Article
- SARS-CoV-2 NSP12 associates with TRiC and the P323L substitution acts as a host adaption.Journal of virology · 2023Article
- Article
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30 authors at 9 institutions in 4 countries.
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Abstract
backgroundThe mutational landscape of SARS-CoV-2 varies at the dominant viral genome sequence and minor genomic variant population. During the COVID-19 pandemic, an early substitution in the genome was the D614G change in the spike protein, associated with an increase in transmissibility. Genomes with D614G are accompanied by a P323L substitution in the viral polymerase (NSP12). However, P323L is not thought to be under strong selective pressure.
resultsInvestigation of P323L/D614G substitutions in the population shows rapid emergence during the containment phase and early surge phase during the first wave. These substitutions emerge from minor genomic variants which become dominant viral genome sequence. This is investigated in vivo and in vitro using SARS-CoV-2 with P323 and D614 in the dominant genome sequence and L323 and G614 in the minor variant population. During infection, there is rapid selection of L323 into the dominant viral genome sequence but not G614. Reverse genetics is used to create two viruses (either P323 or L323) with the same genetic background. L323 shows greater abundance of viral RNA and proteins and a smaller plaque morphology than P323.
conclusionsThese data suggest that P323L is an important contribution in the emergence of variants with transmission advantages. Sequence analysis of viral populations suggests it may be possible to predict the emergence of a new variant based on tracking the frequency of minor variant genomes. The ability to predict an emerging variant of SARS-CoV-2 in the global landscape may aid in the evaluation of medical countermeasures and non-pharmaceutical interventions.
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