ArticlePLoS pathogens2021
Signatures in SARS-CoV-2 spike protein conferring escape to neutralizing antibodies.
Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed.
- Addressing pandemic-wide systematic errors in the SARS-CoV-2 phylogeny.Nature methods · 2026Article
- 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
- Dynamics of neutralizing antibodies against COVID-19 Omicron subvariants following breakthrough infection in southwest China between December 2022 and April 2024.Signal transduction and targeted therapy · 2025Article
- Article
- Pre-existing IgG antibodies to HCoVs NL63 and OC43 Spike increased during the pandemic and after COVID-19 vaccination.Heliyon · 2025Article
- Viral entry mechanisms: the role of molecular simulation in unlocking a key step in viral infections.FEBS open bio · 2025Review
- Addressing pandemic-wide systematic errors in the SARS-CoV-2 phylogeny.bioRxiv : the preprint server for biology · 2024Article
- Profiling serum immunodominance following SARS-CoV-2 primary and breakthrough infection reveals distinct variant-specific epitope usage and immune imprinting.PLoS pathogens · 2024Article
- SARS-CoV-2 variants induce increased inflammatory gene expression but reduced interferon responses and heme synthesis as compared with wild type strains.Scientific reports · 2024Article
- Characterisation of the antibody-mediated selective pressure driving intra-host evolution of SARS-CoV-2 in prolonged infection.PLoS pathogens · 2024Article
- Detection and Characterisation of SARS-CoV-2 in Eastern Province of Zambia: A Retrospective Genomic Surveillance Study.International journal of molecular sciences · 2024Article
- COVID-19 Variants and Vaccine Development.Viruses · 2024Review
- Quantifying how single dose Ad26.COV2.S vaccine efficacy depends on Spike sequence features.Nature communications · 2024Article
- Incipient functional SARS-CoV-2 diversification identified through neural network haplotype maps.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Within-host evolution of SARS-CoV-2: how often areVirus evolution · 2024Article
- Clinical characteristics and novel mutations of omicron subvariant XBB in Tamil Nadu, India - a cohort study.The Lancet regional health. Southeast Asia · 2023Article
- Protection of the receptor binding domain (RBD) dimer against SARS-CoV-2 and its variants.Journal of virology · 2023Article
- Nucleocapsid single point-mutation associated with drop-out on RT-PCR assay for SARS-CoV-2 detection.BMC infectious diseases · 2023Article
- Balance between maternal antiviral response and placental transfer of protection in gestational SARS-CoV-2 infection.JCI insight · 2023Article
- Identification of inhibitors against SARS-CoV-2 variants of concern using virtual screening and metadynamics-based enhanced sampling.Chemical physics · 2023Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Understanding SARS-CoV-2 evolution and host immunity is critical to control COVID-19 pandemics. At the core is an arms-race between SARS-CoV-2 antibody and angiotensin-converting enzyme 2 (ACE2) recognition, a function of the viral protein spike. Mutations in spike impacting antibody and/or ACE2 binding are appearing worldwide, imposing the need to monitor SARS-CoV2 evolution and dynamics in the population. Determining signatures in SARS-CoV-2 that render the virus resistant to neutralizing antibodies is critical. We engineered 25 spike-pseudotyped lentiviruses containing individual and combined mutations in the spike protein, including all defining mutations in the variants of concern, to identify the effect of single and synergic amino acid substitutions in promoting immune escape. We confirmed that E484K evades antibody neutralization elicited by infection or vaccination, a capacity augmented when complemented by K417N and N501Y mutations. In silico analysis provided an explanation for E484K immune evasion. E484 frequently engages in interactions with antibodies but not with ACE2. Importantly, we identified a novel amino acid of concern, S494, which shares a similar pattern. Using the already circulating mutation S494P, we found that it reduces antibody neutralization of convalescent and post-immunization sera, particularly when combined with E484K and with mutations able to increase binding to ACE2, such as N501Y. Our analysis of synergic mutations provides a signature for hotspots for immune evasion and for targets of therapies, vaccines and diagnostics.
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