ArticlePLoS pathogens2021
Mutation Y453F in the spike protein of SARS-CoV-2 enhances interaction with the mink ACE2 receptor for host adaption.
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 53 papers.
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Who cites it
53 citing papers in PubMed, 69 citations in OpenAlex.
- SARS-CoV-2 Delta variant re-emerges in US farmed mink and free-ranging white-tailed deer in 2022-2023.Nature communications · 2026Article
- Bruton's tyrosine kinase inhibitor BTKi-2 inhibits mpox virus and vaccinia virus infection.Virologica Sinica · 2026Article
- Stringent selection drives convergence toward omicron-like SARS-CoV-2 receptor-binding motifs.Nature communications · 2026Article
- Molecular basis of fox ACE2 recognition by receptor binding domains of SARS-CoV-2 and PCoV-GD.Cell insight · 2026Article
- Spike destabilization attenuates Mink Cluster 5 SARS-CoV-2.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Evolution of SARS-CoV-2 caused infection in farmed minks: continuous surveillance of an 11-month outbreak at the largest Latvian mink farm.Virus evolution · 2026Article
- Article
- Insights from deep mutational scanning in the context of an emerging pathogen.Biochemical Society transactions · 2025Review
- Critical amino acid residues in human ACE2 for SARS-CoV-2 spike protein binding and virus entry.Microbiology spectrum · 2025Article
- Vesicle-associated membrane protein 5 is an intrinsic defense factor for embryonic stem cells against coronaviruses.Nature communications · 2025Article
- The recurrent Spike A222V mutation in SARS-CoV-2 enhances replication in primary deer lung cells.Virus evolution · 2025Article
- Features of Highly Homologous T-Cell Receptor Repertoire in the Immune Response to Mutations in Immunogenic Epitopes.International journal of molecular sciences · 2024Article
- Preventing future zoonosis: SARS-CoV-2 mutations enhance human-animal cross-transmission.Computers in biology and medicine · 2024Article
- COVID-19 mutations: An overview.World journal of methodology · 2024Review
- Article
- Structural insights into immune escape at killer T cell epitope by SARS-CoV-2 Spike Y453F variants.The Journal of biological chemistry · 2024Article
- Genome-wide CRISPR/Cas9 screen identifies SLC39A9 and PIK3C3 as crucial entry factors for Ebola virus infection.PLoS pathogens · 2024Article
- Emergence and spread of SARS-CoV-2 variants from farmed mink to humans and back during the epidemic in Denmark, June-November 2020.PLoS pathogens · 2024Article
- Genomic Context of SARS-CoV-2 Outbreaks in Farmed Mink in Spain during Pandemic: Unveiling Host Adaptation Mechanisms.International journal of molecular sciences · 2024Article
- COVID-19 Variants and Vaccine Development.Viruses · 2024Review
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Authors and funding
15 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
COVID-19 patients transmitted SARS-CoV-2 to minks in the Netherlands in April 2020. Subsequently, the mink-associated virus (miSARS-CoV-2) spilled back over into humans. Genetic sequences of the miSARS-CoV-2 identified a new genetic variant known as "Cluster 5" that contained mutations in the spike protein. However, the functional properties of these "Cluster 5" mutations have not been well established. In this study, we found that the Y453F mutation located in the RBD domain of miSARS-CoV-2 is an adaptive mutation that enhances binding to mink ACE2 and other orthologs of Mustela species without compromising, and even enhancing, its ability to utilize human ACE2 as a receptor for entry. Structural analysis suggested that despite the similarity in the overall binding mode of SARS-CoV-2 RBD to human and mink ACE2, Y34 of mink ACE2 was better suited to interact with a Phe rather than a Tyr at position 453 of the viral RBD due to less steric clash and tighter hydrophobic-driven interaction. Additionally, the Y453F spike exhibited resistance to convalescent serum, posing a risk for vaccine development. Thus, our study suggests that since the initial transmission from humans, SARS-CoV-2 evolved to adapt to the mink host, leading to widespread circulation among minks while still retaining its ability to efficiently utilize human ACE2 for entry, thus allowing for transmission of the miSARS-CoV-2 back into humans. These findings underscore the importance of active surveillance of SARS-CoV-2 evolution in Mustela species and other susceptible hosts in order to prevent future outbreaks.
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