ArticleNature communications2021
SARS-CoV-2 gene content and COVID-19 mutation impact by comparing 44 Sarbecovirus genomes.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers.
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Who cites it
125 citing papers in PubMed, 173 citations in OpenAlex.
- Functional Effects of Receptor-Binding Domain Mutations of SARS-CoV-2 B.1.351 and P.1 Variants.Frontiers in immunology · 2021Trial
- Extra gene coding capacity of SARS-CoV-2 provides a virus engineering platform for in vitro and in vivo applications.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- SARS-CoV-2 Spike Protein's Structural Dynamics Affect the Activity of the Bebtelovimab Antibody.Journal of chemical information and modeling · 2026Article
- Development of a Thermostable and Broadly Neutralizing Pan-Sarbecovirus Vaccine Candidate.ACS infectious diseases · 2026Article
- SARS-CoV-2-host and interactions: the dual roles of E3 ubiquitin ligases and ubiquitin-like modification mechanisms in viral infection.Frontiers in immunology · 2026Review
- Mouse-adapted SARS-CoV-2 Omicron BA.5 infection induces post-acute lung fibrosis in BALB/c mice.Journal of virology · 2025Article
- A Novel Fluorescence Polarization Binding Assay for the Main Protease (MACS pharmacology & translational science · 2025Article
- Mouse Adapted Omicron BA.5 Induces A Fibrotic Lung Disease Phenotype in BALB/c Mice.bioRxiv : the preprint server for biology · 2025Article
- Review
- Examining the feasibility of replacing ORF3a with fluorescent genes to construct SARS-CoV-2 reporter viruses.The Journal of general virology · 2025Article
- Barcoded SARS-CoV-2 viruses define the impact of duration and route of exposure on the transmission bottleneck in a hamster model.Science advances · 2025Article
- Non-spike protein inhibition of SARS-CoV-2 by natural products through the key mediator protein ORF8.Molecular biology research communications · 2025Article
- Hidden players of COVID-19: the evolving roles of SARS-CoV-2 accessory proteins.Frontiers in immunology · 2025Review
- Patterns of Isoform Variation for N Gene Subgenomic mRNAs in Betacoronavirus Transcriptomes.Viruses · 2024Article
- In Silico Identification of Potential Inhibitors of SARS-CoV-2 Main Protease (MPathogens (Basel, Switzerland) · 2024Article
- Heterotypic immunity from prior SARS-CoV-2 infection but not COVID-19 vaccination associates with lower endemic coronavirus incidence.Science translational medicine · 2024Article
- Article
- SARS-CoV-2 resistance to monoclonal antibodies and small-molecule drugs.Cell chemical biology · 2024Review
- SARS-CoV-2 biology and host interactions.Nature reviews. Microbiology · 2024Review
- Preclinical Development of a Novel Epitope-based DNA Vaccine Candidate against SARS-CoV-2 and Evaluation of Immunogenicity in BALB/c Mice.AAPS PharmSciTech · 2024Article
65 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Despite its clinical importance, the SARS-CoV-2 gene set remains unresolved, hindering dissection of COVID-19 biology. We use comparative genomics to provide a high-confidence protein-coding gene set, characterize evolutionary constraint, and prioritize functional mutations. We select 44 Sarbecovirus genomes at ideally-suited evolutionary distances, and quantify protein-coding evolutionary signatures and overlapping constraint. We find strong protein-coding signatures for ORFs 3a, 6, 7a, 7b, 8, 9b, and a novel alternate-frame gene, ORF3c, whereas ORFs 2b, 3d/3d-2, 3b, 9c, and 10 lack protein-coding signatures or convincing experimental evidence of protein-coding function. Furthermore, we show no other conserved protein-coding genes remain to be discovered. Mutation analysis suggests ORF8 contributes to within-individual fitness but not person-to-person transmission. Cross-strain and within-strain evolutionary pressures agree, except for fewer-than-expected within-strain mutations in nsp3 and S1, and more-than-expected in nucleocapsid, which shows a cluster of mutations in a predicted B-cell epitope, suggesting immune-avoidance selection. Evolutionary histories of residues disrupted by spike-protein substitutions D614G, N501Y, E484K, and K417N/T provide clues about their biology, and we catalog likely-functional co-inherited mutations. Previously reported RNA-modification sites show no enrichment for conservation. Here we report a high-confidence gene set and evolutionary-history annotations providing valuable resources and insights on SARS-CoV-2 biology, mutations, and evolution.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.