Multivalent and De Novo Miniprotein Inhibitors Targeting SARS-CoV-2 Spike Protein
This suite of protein-based inhibitors is designed to block SARS-CoV-2 infection by binding to the virus’s spike protein with high precision. The technologies include multivalent constructs and de novo miniproteins that neutralize diverse variants and offer potential for intranasal delivery.
What is the Problem?
Despite widespread vaccination efforts, SARS-CoV-2 continues to circulate globally, with new variants emerging that can partially evade immune responses. Existing antiviral treatments often rely on monoclonal antibodies, which are costly to produce and may lose effectiveness as the virus evolves. There is a need for alternative therapeutics that are stable, scalable, and adaptable to variant changes. Additionally, delivery methods that target the respiratory tract directly could improve accessibility and efficacy.
What is the Solution?
This technology suite offers a series of protein-based inhibitors that bind tightly to the SARS-CoV-2 spike protein, preventing the virus from attaching to human cells. These include:
-De novo miniproteins, which are small, synthetic proteins designed from scratch to mimic the virus’s natural receptor (ACE2) and block viral entry.
-Multivalent minibinders, which link multiple binding domains together to engage several sites on the spike protein simultaneously, increasing potency and resilience against mutations.
These inhibitors have demonstrated picomolar binding affinity—meaning they are highly effective at very low concentrations—and have shown protective effects in animal models. Some constructs are suitable for intranasal delivery, offering a non-invasive route for prophylactic or therapeutic use.
What is the Competitive Advantage?
-High binding affinity: Engineered to bind the spike protein more tightly than natural receptors or many antibodies.
-Variant resilience: Multivalent designs maintain neutralization across multiple SARS-CoV-2 variants.
-Scalable production: Small protein size and cell-free expression systems support rapid and cost-effective manufacturing.
-Flexible delivery: Intranasal formulations enable direct targeting of the respiratory tract without injections.
-Synthetic design: De novo proteins are not derived from human or animal sources, reducing immunogenicity and allowing precise control over structure and function.
Patent Information:
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expand_more mode_edit Authors (1)David Baker
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expand_more library_books References (2)
- Hunt, A. C., Case, J. B., Park, Y. J., Cao, L., Wu, K., Walls, A. C., Liu, Z., Bowen, J. E., Yeh, H. W., Saini, S., Helms, L., Zhao, Y. T., Hsiang, T. Y., Starr, T. N., Goreshnik, I., Kozodoy, L., Carter, L., Ravichandran, R., Green, L. B., Matochko, W. L., Thomson, C. A., Vögeli, B., Krüger, A., VanBlargan, L. A., Chen, R. E., Ying, B., Bailey, A. L., Kafai, N. M., Boyken, S. E., Ljubetič, A., Edman, N., Ueda, G., Chow, C. M., Johnson, M., Addetia, A., Navarro, M. J., Panpradist, N., Gale, M., Jr., Freedman, B. S., Bloom, J. D., Ruohola-Baker, H., Whelan, S. P. J., Stewart, L., Diamond, M. S., Veesler, D., Jewett, M. C., Baker, D. (2022), Multivalent designed proteins neutralize SARS-CoV-2 variants of concern and confer protection against infection in mice, Science Translational Medicine, 14, eabn1252
- Cao, L., Goreshnik, I., Coventry, B., Case, J. B., Miller, L., Kozodoy, L., Chen, R. E., Carter, L., Walls, A. C., Park, Y. J., Strauch, E. M., Stewart, L., Diamond, M. S., Veesler, D., Baker, D. (2020), De novo design of picomolar SARS-CoV-2 miniprotein inhibitors, Science, 370, 426-431
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expand_more cloud_download Supporting documents (1)Product brochureMultivalent and De Novo Miniprotein Inhibitors Targeting SARS-CoV-2 Spike Protein.pdf