ArticlePLoS pathogens2022
In vitro evolution predicts emerging SARS-CoV-2 mutations with high affinity for ACE2 and cross-species binding.
Article in PLoS pathogens, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
38 citing papers in PubMed, 56 citations in OpenAlex.
- Functional and structural characterization of the SARS-CoV-2 spike N481K mutation.Archives of virology · 2026Article
- Stringent selection drives convergence toward omicron-like SARS-CoV-2 receptor-binding motifs.Nature communications · 2026Article
- Antibody escape drives emergence of diverse spike haplotypes resembling variants of concern in persistent SARS-CoV-2 infections.Cell reports. Medicine · 2026Article
- Review
- A highly divergent cryptic SARS-CoV-2 lineage exhibits strong receptor binding and immune evasion.medRxiv : the preprint server for health sciences · 2025Article
- Insights from deep mutational scanning in the context of an emerging pathogen.Biochemical Society transactions · 2025Review
- SARS-CoV-2 Evolution in Humans Enables Its Transmission to Nonhuman Primates.Molecular biology and evolution · 2025Article
- A single mutation may contribute to accelerated evolution of SARS-CoV-2 toward Omicron.Nature communications · 2025Article
- Mutational pressure promotes release of public CD8iScience · 2025Article
- Article
- Ongoing evolution of SARS-CoV-2 drives escape from mRNA vaccine-induced humoral immunity.Cell reports. Medicine · 2024Article
- Interfacial subregions of SARS-CoV-2 spike RBD to hACE2 affect intermolecular affinity by their distinct roles played in association and dissociation kinetics.Communications biology · 2024Article
- Preventing future zoonosis: SARS-CoV-2 mutations enhance human-animal cross-transmission.Computers in biology and medicine · 2024Article
- Article
- Review
- Studying SARS-CoV-2 interactions using phage-displayed receptor binding domain as a model protein.Scientific reports · 2024Article
- Deep mutational scans of XBB.1.5 and BQ.1.1 reveal ongoing epistatic drift during SARS-CoV-2 evolution.PLoS pathogens · 2023Article
- SARS-CoV-2 genomic surveillance in wastewater as a model for monitoring evolution of endemic viruses.Nature communications · 2023Article
- Deep mutational scans of XBB.1.5 and BQ.1.1 reveal ongoing epistatic drift during SARS-CoV-2 evolution.bioRxiv : the preprint server for biology · 2023Article
- COVID Variants, Villain and Victory: A Bioinformatics Perspective.Microorganisms · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Emerging SARS-CoV-2 variants are creating major challenges in the ongoing COVID-19 pandemic. Being able to predict mutations that could arise in SARS-CoV-2 leading to increased transmissibility or immune evasion would be extremely valuable in development of broad-acting therapeutics and vaccines, and prioritising viral monitoring and containment. Here we use in vitro evolution to seek mutations in SARS-CoV-2 receptor binding domain (RBD) that would substantially increase binding to ACE2. We find a double mutation, S477N and Q498H, that increases affinity of RBD for ACE2 by 6.5-fold. This affinity gain is largely driven by the Q498H mutation. We determine the structure of the mutant-RBD:ACE2 complex by cryo-electron microscopy to reveal the mechanism for increased affinity. Addition of Q498H to SARS-CoV-2 RBD variants is found to boost binding affinity of the variants for human ACE2 and confer a new ability to bind rat ACE2 with high affinity. Surprisingly however, in the presence of the common N501Y mutation, Q498H inhibits binding, due to a clash between H498 and Y501 side chains. To achieve an intermolecular bonding network, affinity gain and cross-species binding similar to Q498H alone, RBD variants with the N501Y mutation must acquire instead the related Q498R mutation. Thus, SARS-CoV-2 RBD can access large affinity gains and cross-species binding via two alternative mutational routes involving Q498, with route selection determined by whether a variant already has the N501Y mutation. These mutations are now appearing in emerging SARS-CoV-2 variants where they have the potential to influence human-to-human and cross-species transmission.
Indexed as
Identifiers
What OpenQuestion holds
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.