Academic Journal
Neutralization of SARS-CoV‑2 and Intranasal Protection of Mice with a nanoCLAMP Antibody Mimetic
| العنوان: | Neutralization of SARS-CoV‑2 and Intranasal Protection of Mice with a nanoCLAMP Antibody Mimetic |
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| المؤلفون: | Quentin Pagneux, Nathalie Garnier, Manon Fabregue, Sarah Sharkaoui, Sophie Mazzoli, Ilka Engelmann, Rabah Boukherroub, Mary Strecker, Eric Cruz, Peter Ducos, Sabine Szunerits, Ana Zarubica, Richard Suderman |
| سنة النشر: | 2024 |
| مصطلحات موضوعية: | Biophysics, Biochemistry, Medicine, Microbiology, Molecular Biology, Pharmacology, Evolutionary Biology, Ecology, Immunology, Cancer, Infectious Diseases, Virology, slow mutational evolution, reduced viral loads, reduced associated upregulation, p2712 potently inhibited, intranasally administered therapeutic, 4 ± 0, pm affinity single, 1 nm obtained, 50 , cov ‑ 2, pm affinity, 7 nm, k <, decreasing affinity, , 86 pm, 1 pm, south african |
| الوصف: | Intranasal treatment, combined with vaccination, has the potential to slow mutational evolution of viruses by reducing transmission and replication. Here, we illustrate the development of a SARS-CoV-2 receptor-binding domain (RBD) nanoCLAMP and demonstrate its potential as an intranasally administered therapeutic. A multi-epitope nanoCLAMP was made by fusing a pM affinity single-domain nanoCLAMP (P2710) to alternate epitope-binding nanoCLAMP, P2609. The resulting multimerized nanoCLAMP P2712 had sub-pM affinity for the Wuhan and South African (B.1.351) RBD ( K D < 1 pM) and decreasing affinity for the Delta (B.1.617.2) and Omicron (B.1.1.529) variants (86 pM and 19.7 nM, respectively). P2712 potently inhibited the ACE2:RBD interaction, suggesting its utility as a therapeutic. With an IC 50 = 0.4 ± 0.1 nM obtained from neutralization experiments using pseudoviral particles, nanoCLAMP P2712 protected K18-hACE2 mice from SARS-CoV-2 infection, reduced viral loads in the lungs and brains, and reduced associated upregulation of inflammatory cytokines and chemokines. Together, our findings warrant further investigation into the development of nanoCLAMPs as effective intranasally delivered COVID-19 therapeutics. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| Relation: | https://figshare.com/articles/journal_contribution/Neutralization_of_SARS-CoV_2_and_Intranasal_Protection_of_Mice_with_a_nanoCLAMP_Antibody_Mimetic/25127347 |
| DOI: | 10.1021/acsptsci.3c00306.s001 |
| الاتاحة: | https://doi.org/10.1021/acsptsci.3c00306.s001 https://figshare.com/articles/journal_contribution/Neutralization_of_SARS-CoV_2_and_Intranasal_Protection_of_Mice_with_a_nanoCLAMP_Antibody_Mimetic/25127347 |
| Rights: | CC BY-NC 4.0 |
| رقم الانضمام: | edsbas.EF8D8C2 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1021/acsptsci.3c00306.s001 |
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