ArticleCell reports2023
SARS-CoV-2 variants with NSP12 P323L/G671S mutations display enhanced virus replication in ferret upper airways and higher transmissibility.
Article in Cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Back to the wildtype: SARS-CoV-2 evolution in critically ill patients with severe lung failure.Infection · 2026Article
- SARS-CoV-2 variants: biology, pathogenicity, immunity and control.Nature reviews. Microbiology · 2026Review
- 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
- RNA Binding Sensitivity of Nonstructural Protein 8 Revealed by Small-Angle Neutron Scattering and Alphafold2 Prediction.ACS nano · 2025Article
- Therapeutic applications of interface-mimicking peptides for targeting the SARS-CoV-2 NSP12-NSP8 RdRp complex.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Substitution-Mutation Rate Ratio (c/µ) As Molecular Adaptation Test Beyond Ka/Ks: A SARS-COV-2 Case Study.Journal of molecular evolution · 2025Article
- A post-assembly conformational change makes the SARS-CoV-2 polymerase elongation-competent.Nucleic acids research · 2025Article
- A Phylogenetic Method Identifies Candidate Drivers of the Evolution of the SARS-CoV-2 Mutation Spectrum.Molecular biology and evolution · 2025Article
- Enhanced RNA replication and pathogenesis in recent SARS-CoV-2 variants harboring the L260F mutation in NSP6.PLoS pathogens · 2025Article
- A comprehensive review of current insights into the virulence factors of SARS-CoV-2.Journal of virology · 2025Review
- The impact of remdesivir on SARS-CoV-2 evolution in vivo.JCI insight · 2025Article
- A phylogenetic method identifies candidate drivers of the evolution of the SARS-CoV-2 mutation spectrum.bioRxiv : the preprint server for biology · 2025Article
- SARS-CoV-2 evolution enhances endocytic uptake while preserving TMPRSS2-dependent fusion.Frontiers in immunology · 2025Article
- SARS-CoV-2 Evolution: Implications for Diagnosis, Treatment, Vaccine Effectiveness and Development.Vaccines · 2024Review
- 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
- Point mutations at specific sites of the nsp12-nsp8 interface dramatically affect the RNA polymerization activity of SARS-CoV-2.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- Enhanced detection and molecular modeling of adaptive mutations in SARS-CoV-2 coding and non-coding regions using the c/µ test.Virus evolution · 2024Article
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21 authors.
Funding
Abstract
With the emergence of multiple predominant SARS-CoV-2 variants, it becomes important to have a comprehensive assessment of their viral fitness and transmissibility. Here, we demonstrate that natural temperature differences between the upper (33°C) and lower (37°C) respiratory tract have profound effects on SARS-CoV-2 replication and transmissibility. Specifically, SARS-CoV-2 variants containing the NSP12 mutations P323L or P323L/G671S exhibit enhanced RNA-dependent RNA polymerase (RdRp) activity at 33°C compared with 37°C and high transmissibility. Molecular dynamics simulations and microscale thermophoresis demonstrate that the NSP12 P323L and P323L/G671S mutations stabilize the NSP12-NSP7-NSP8 complex through hydrophobic effects, leading to increased viral RdRp activity. Furthermore, competitive transmissibility assay reveals that reverse genetic (RG)-P323L or RG-P323L/G671S NSP12 outcompetes RG-WT (wild-type) NSP12 for replication in the upper respiratory tract, allowing markedly rapid transmissibility. This suggests that NSP12 P323L or P323L/G671S mutation of SARS-CoV-2 is associated with increased RdRp complex stability and enzymatic activity, promoting efficient transmissibility.
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