Multivalent designed proteins neutralize SARS-CoV-2 variants of concern and confer protection against infection in mice

Message boards : Rosetta@home Science : Multivalent designed proteins neutralize SARS-CoV-2 variants of concern and confer protection against infection in mice

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Rosetta_Folder

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Message 105933 - Posted: 14 Apr 2022, 9:51:21 UTC

New variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to arise and prolong the coronavirus disease 2019 (COVID-19) pandemic. Here we used a cell-free expression workflow to rapidly screen and optimize constructs containing multiple computationally designed miniprotein inhibitors of SARS-CoV-2. We found the broadest efficacy with a homo-trimeric version of the 75-residue angiotensin converting enzyme 2 (ACE2) mimic AHB2 (TRI2-2) designed to geometrically match the trimeric spike architecture. In the cryo-electron microscopy structure, TRI2 formed a tripod on top of the spike protein which engaged all three receptor binding domains (RBDs) simultaneously as in the design model. TRI2-2 neutralized Omicron (B.1.1.529), Delta (B.1.617.2), and all other variants tested with greater potency than that of monoclonal antibodies used clinically for the treatment of COVID-19. TRI2-2 also conferred prophylactic and therapeutic protection against SARS-CoV-2 challenge when administered intranasally in mice. Designed miniprotein receptor mimics geometrically arrayed to match pathogen receptor binding sites could be a widely applicable antiviral therapeutic strategy with advantages over antibodies and native receptor traps. By comparison, the designed proteins have resistance to viral escape and antigenic drift by construction, precisely tuned avidity, and greatly reduced chance of autoimmune responses.


https://www.science.org/doi/10.1126/scitranslmed.abn1252
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Jim1348

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Message 105935 - Posted: 14 Apr 2022, 14:13:22 UTC - in response to Message 105933.  

Thanks. I knew they had been working on that earlier, but hadn't heard from them in a long time and I didn't know if they were still doing it.
It looks like they are going full guns. They can do great things with their technique.
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Rosetta_Folder

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Message 105938 - Posted: 14 Apr 2022, 20:35:15 UTC - in response to Message 105935.  

Thanks. I knew they had been working on that earlier, but hadn't heard from them in a long time and I didn't know if they were still doing it.
It looks like they are going full guns. They can do great things with their technique.


Yeah, I'm at least as excited for their tech as I am for mRNA.
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Message boards : Rosetta@home Science : Multivalent designed proteins neutralize SARS-CoV-2 variants of concern and confer protection against infection in mice



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