作者
Andrew C Hunt, James Brett Case, Young-Jun Park, Longxing Cao, Kejia Wu, Alexandra C Walls, Zhuoming Liu, John E Bowen, Hsien-Wei Yeh, Shally Saini, Louisa Helms, Yan Ting Zhao, Tien-Ying Hsiang, Tyler N Starr, Inna Goreshnik, Lisa Kozodoy, Lauren Carter, Rashmi Ravichandran, Lydia B Green, Wadim L Matochko, Christy A Thomson, Bastian Vögeli, Antje Krüger, Laura A VanBlargan, Rita E Chen, Baoling Ying, Adam L Bailey, Natasha M Kafai, Scott E Boyken, Ajasja Ljubetič, Natasha Edman, George Ueda, Cameron M Chow, Max Johnson, Amin Addetia, Mary-Jane Navarro, Nuttada Panpradist, Michael Gale Jr, Benjamin S Freedman, Jesse D Bloom, Hannele Ruohola-Baker, Sean PJ Whelan, Lance Stewart, Michael S Diamond, David Veesler, Michael C Jewett, David Baker
发表日期
2022/4/12
期刊
Science translational medicine
卷号
14
期号
646
页码范围
eabn1252
出版商
American Association for the Advancement of Science
简介
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 was achieved with a homotrimeric version of the 75-residue angiotensin-converting enzyme 2 (ACE2) mimic AHB2 (TRI2-2) designed to geometrically match the trimeric spike architecture. Consistent with the design model, in the cryo-electron microscopy structure TRI2-2 forms a tripod at the apex of the spike protein that engaged all three receptor binding domains simultaneously. TRI2-2 neutralized Omicron (B.1.1.529), Delta (B.1.617.2), and all other variants tested with greater potency than the monoclonal antibodies used clinically for the treatment …
学术搜索中的文章
AC Hunt, JB Case, YJ Park, L Cao, K Wu, AC Walls… - Science translational medicine, 2022