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Ultrapotent miniproteins targeting the SARS-CoV-2 receptor-binding domain protect against infection and disease

Cell Host Microbe. 2021-06; 
James Brett Case, Rita E Chen, Longxing Cao, Baoling Ying, Emma S Winkler, Max Johnson, Inna Goreshnik, Minh N Pham, Swathi Shrihari, Natasha M Kafai, Adam L Bailey, Xuping Xie, Pei-Yong Shi, Rashmi Ravichandran, Lauren Carter, Lance Stewart, David Baker, Michael S Diamond
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Bacterial Expression … LCB1-Fc was synthesized and cloned by GenScript into pCMVR plasmid, with kanamycin resistance. Plasmids were transformed into the NEB 5-alpha strain of E. coli (New England Biolabs) to recover DNA for transient transfection into Expi293F mammalian cells. … Get A Quote

摘要

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... More

关键词

COVID-19, SARS-CoV-2, intranasal, mice, miniprotein, pathogenesis, prophylaxis, receptor-binding domain, therapy, variants