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Ultrapotent miniproteins targeting the SARS-CoV-2 receptor-binding domain protect against infection and disease #MMPMID34192518
Case JB; Chen RE; Cao L; Ying B; Winkler ES; Johnson M; Goreshnik I; Pham MN; Shrihari S; Kafai NM; Bailey AL; Xie X; Shi PY; Ravichandran R; Carter L; Stewart L; Baker D; Diamond MS
Cell Host Microbe 2021[Jul]; 29 (7): 1151-1161.e5 PMID34192518show ga
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 5 days before or 2 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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Cell+Host+Microbe 2021 ; 29 (7): 1151-1161.e5
