ArticleScientific reports2021
Concurrent mutations in RNA-dependent RNA polymerase and spike protein emerged as the epidemiologically most successful SARS-CoV-2 variant.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 78 citations in OpenAlex.
- Diversity and distinctive characteristics of the global RNA virome in urban and peri-urban environments.Nature communications · 2026Article
- Predicting the evolution and persistence of COVID-19 using context-dependent polymorphisms.Scientific reports · 2026Article
- 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
- deepBreaks identifies and prioritizes genotype-phenotype associations using machine learning.Scientific reports · 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
- Hypericin Suppresses SARS-CoV-2 Replication and Synergizes with Antivirals via Dual Targeting of RdRp and 3CLpro.Microorganisms · 2025Article
- Strong evidence for the evolution of decreasing compositional heterogeneity in SARS-CoV-2 genomes during the pandemic.Scientific reports · 2025Article
- A comprehensive review of current insights into the virulence factors of SARS-CoV-2.Journal of virology · 2025Review
- Progressive Evolutionary Dynamics of Gene-Specific ω Led to the Emergence of Novel SARS-CoV-2 Strains Having Super-Infectivity and Virulence with Vaccine Neutralization.International journal of molecular sciences · 2024Article
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- Emergence of SARS-CoV-2 Variants Are Induced by Coinfections With Dengue.Bioinformatics and biology insights · 2024Article
- Novel sofosbuvir derivatives against SARS-CoV-2 RNA-dependent RNA polymerase: an in silico perspective.Scientific reports · 2023Article
- Assessing Genomic Mutations in SARS-CoV-2: Potential Resistance to Antiviral Drugs in Viral Populations from Untreated COVID-19 Patients.Microorganisms · 2023Article
- SARS-CoV-2 NSP12 associates with TRiC and the P323L substitution acts as a host adaption.Journal of virology · 2023Article
- Review
- Molecular and Structural Aspects of Clinically Relevant Mutations of SARS-CoV-2 RNA-Dependent RNA Polymerase in Remdesivir-Treated Patients.Pharmaceuticals (Basel, Switzerland) · 2023Article
- SARS-CoV-2 Variants by Whole-Genome Sequencing in a University Hospital in Bangkok: First to Third COVID-19 Waves.Pathogens (Basel, Switzerland) · 2023Article
- The P323L substitution in the SARS-CoV-2 polymerase (NSP12) confers a selective advantage during infection.Genome biology · 2023Article
- Effects of natural polymorphisms in SARS-CoV-2 RNA-dependent RNA polymerase on its activity and sensitivity to inhibitors in vitro.Biochimie · 2023Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The D614G mutation in the Spike protein of the SARS-CoV-2 has effectively replaced the early pandemic-causing variant. Using pseudotyped lentivectors, we confirmed that the aspartate replacement by glycine in position 614 is markedly more infectious. Molecular modelling suggests that the G614 mutation facilitates transition towards an open state of the Spike protein. To explain the epidemiological success of D614G, we analysed the evolution of 27,086 high-quality SARS-CoV-2 genome sequences from GISAID. We observed striking coevolution of D614G with the P323L mutation in the viral polymerase. Importantly, the exclusive presence of G614 or L323 did not become epidemiologically relevant. In contrast, the combination of the two mutations gave rise to a viral G/L variant that has all but replaced the initial D/P variant. Our results suggest that the P323L mutation, located in the interface domain of the RNA-dependent RNA polymerase, is a necessary alteration that led to the epidemiological success of the present variant of SARS-CoV-2. However, we did not observe a significant correlation between reported COVID-19 mortality in different countries and the prevalence of the Wuhan versus G/L variant. Nevertheless, when comparing the speed of emergence and the ultimate predominance in individual countries, it is clear that the G/L variant displays major epidemiological supremacy over the original variant.
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