ArticleNature microbiology2021
SARS-CoV-2 variant prediction and antiviral drug design are enabled by RBD in vitro evolution.
Article in Nature microbiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 254 papers, 1 of them a synthesis that pooled it.
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
254 citing papers in PubMed, 1 synthesis or guideline pooled it, 418 citations in OpenAlex.
- Effect of sofosbuvir-based treatment on clinical outcomes of patients with COVID-19: a systematic review and meta-analysis of randomised controlled trials.International journal of antimicrobial agents · 2022Pooled it
- Randomized controlled trial of molnupiravir SARS-CoV-2 viral and antibody response in at-risk adult outpatients.Nature communications · 2024Trial
- Deep mutational scanning of recent SARS-CoV-2 variants highlights changing amino acid preferences within epistatic hotspot residues.PLoS pathogens · 2026Article
- Stringent selection drives convergence toward omicron-like SARS-CoV-2 receptor-binding motifs.Nature communications · 2026Article
- Genome characterization of the SARS-CoV-2 omicron in Cameroon.BMC infectious diseases · 2026Article
- Discovery of thiadiazole-based small-molecule inhibitors of SARS-CoV-2 spike-ACE2 interaction through integrated computational prediction and experimental validation.Scientific reports · 2026Article
- Designing a novel vaccine against COVID-19 based on spike SARS-Cov-2 notable mutations using immunoinformatics approaches.PloS one · 2026Article
- Chronic infections can generate SARS-CoV-2-like bursts of viral evolution without epistasis.Virus evolution · 2026Article
- Characterization of the heterogeneity in SARS-CoV-2 fitness dynamics via graph representation learning.PLoS computational biology · 2026Article
- Article
- A public health perspective of SARS-CoV-2 evolution and surveillance strategies in Germany from 2020 to 2023.Communications medicine · 2025Review
- Graph attention with structural features improves the generalizability of identifying functional sequences at a protein interface.bioRxiv : the preprint server for biology · 2025Article
- Modeling the Mutational Effects on Biochemical Phenotypes of SARS-CoV-2 Using Molecular Fields.Biomolecules · 2025Article
- Intra-host SARS-CoV-2 diversity in immunocompromised people living with HIV provides insight into the evolutionary trajectory of SARS-CoV-2.Journal of virology · 2025Article
- Predicting the trend of SARS-CoV-2 mutation frequencies using historical data.Bioinformatics (Oxford, England) · 2025Article
- What Has SARS-CoV-2 Taught Us About Evolution?Cureus · 2025Review
- Molecular mechanisms of SARS-CoV-2 entry: implications for biomedical strategies.Microbiology and molecular biology reviews : MMBR · 2025Review
- CX1/BtSY2 and BANAL-20-52 exhibit broader receptor binding and higher affinities to multiple animal ACE2 orthologs than SARS-CoV-2 prototype.Journal of virology · 2025Article
- An Italian Single-Center Genomic Surveillance Study: Two-Year Analysis of SARS-CoV-2 Spike Protein Mutations.International journal of molecular sciences · 2025Article
- Low-Background His-Tag-Targeting Probes for Turn-On Fluorescence Detection of Cell Surface Proteins and Their Binding Interactions.Small (Weinheim an der Bergstrasse, Germany) · 2025Article
194 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 5 institutions in 3 countries.
Funding
Abstract
SARS-CoV-2 variants of interest and concern will continue to emerge for the duration of the COVID-19 pandemic. To map mutations in the receptor-binding domain (RBD) of the spike protein that affect binding to angiotensin-converting enzyme 2 (ACE2), the receptor for SARS-CoV-2, we applied in vitro evolution to affinity-mature the RBD. Multiple rounds of random mutagenic libraries of the RBD were sorted against decreasing concentrations of ACE2, resulting in the selection of higher affinity RBD binders. We found that mutations present in more transmissible viruses (S477N, E484K and N501Y) were preferentially selected in our high-throughput screen. Evolved RBD mutants include prominently the amino acid substitutions found in the RBDs of B.1.620, B.1.1.7 (Alpha), B1.351 (Beta) and P.1 (Gamma) variants. Moreover, the incidence of RBD mutations in the population as presented in the GISAID database (April 2021) is positively correlated with increased binding affinity to ACE2. Further in vitro evolution increased binding by 1,000-fold and identified mutations that may be more infectious if they evolve in the circulating viral population, for example, Q498R is epistatic to N501Y. We show that our high-affinity variant RBD-62 can be used as a drug to inhibit infection with SARS-CoV-2 and variants Alpha, Beta and Gamma in vitro. In a model of SARS-CoV-2 challenge in hamster, RBD-62 significantly reduced clinical disease when administered before or after infection. A 2.9 Å cryo-electron microscopy structure of the high-affinity complex of RBD-62 and ACE2, including all rapidly spreading mutations, provides a structural basis for future drug and vaccine development and for in silico evaluation of known antibodies.
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.