Author: Case, James Brett; Chen, Rita E.; Cao, Longxing; Ying, Baoling; Winkler, Emma S.; Johnson, Max; Goreshnik, Inna; Pham, Minh N.; Shrihari, Swathi; Kafai, Natasha M.; Bailey, Adam L.; Xie, Xuping; Shi, Pei-Yong; Ravichandran, Rashmi; Carter, Lauren; Stewart, Lance; Baker, David; Diamond, Michael S.
Title: Ultrapotent miniproteins targeting the SARS-CoV-2 receptor-binding domain protect against infection and disease Cord-id: 02bkx2x3 Document date: 2021_6_24
ID: 02bkx2x3
Snippet: Despite the introduction of public health measures and spike protein-based vaccines to mitigate the COVID-19 pandemic, SARS-CoV-2 infections and deaths continue to have a global impact. Previously, we used a structural design approach to develop picomolar range miniproteins targeting the SARS-CoV-2 spike receptor binding domain. Here, we investigated the capacity of modified versions of one lead miniprotein, LCB1, to protect against SARS-CoV-2-mediated lung disease in mice. Systemic administrati
Document: Despite the introduction of public health measures and spike protein-based vaccines to mitigate the COVID-19 pandemic, SARS-CoV-2 infections and deaths continue to have a global impact. Previously, we used a structural design approach to develop picomolar range miniproteins targeting the SARS-CoV-2 spike receptor binding domain. Here, we investigated the capacity of modified versions of one lead miniprotein, LCB1, to protect against SARS-CoV-2-mediated lung disease in mice. Systemic administration of LCB1-Fc reduced viral burden, diminished immune cell infiltration and inflammation, and completely prevented lung disease and pathology. A single intranasal dose of LCB1v1.3 reduced SARS-CoV-2 infection in the lung when given as many as five days before or two days after virus inoculation. Importantly, LCB1v1.3 protected in vivo against a historical strain (WA1/2020), an emerging B.1.1.7 strain, and a strain encoding key E484K and N501Y spike protein substitutions. These data support development of LCB1v1.3 for prevention or treatment of SARS-CoV-2 infection.
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