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 Send message Joined: 16 Dec 21 Posts: 10 Credit: 90,448 RAC: 10 |
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 |
Jim1348 Send message Joined: 19 Jan 06 Posts: 881 Credit: 52,257,545 RAC: 0 |
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. |
Rosetta_Folder Send message Joined: 16 Dec 21 Posts: 10 Credit: 90,448 RAC: 10 |
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. Yeah, I'm at least as excited for their tech as I am for mRNA. |
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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