美国Neoleukin疗法公司Daniel-Adriano Silva研究小组实现抗SARS-CoV-2强效中和性hACE2的从头设计。2020年11月5日，《科学》在线发表了这一成果。

Title: De novo design of potent and resilient hACE2 decoys to neutralize SARS-CoV-2

Author: Thomas W. Linsky, Renan Vergara, Nuria Codina, Jorgen W. Nelson, Matthew J. Walker, Wen Su, Christopher O. Barnes, Tien-Ying Hsiang, Katharina Esser-Nobis, Kevin Yu, Z. Beau Reneer, Yixuan J. Hou, Tanu Priya, Masaya Mitsumoto, Avery Pong, Uland Y. Lau, Marsha L. Mason, Jerry Chen, Alex Chen, Tania Berrocal, Hong Peng, Nicole S. Clairmont, Javier Castellanos, Yu-Ru Lin, Anna Josephson-Day, Ralph S. Baric, Deborah H. Fuller, Carl D. Walkey, Ted M. Ross, Ryan Swanson, Pamela J. Bjorkman, Michael Gale, Luis M. Blancas-Mejia, Hui-Ling Yen, Daniel-Adriano Silva

Issue&Volume: 2020/11/05

Abstract: We developed a de novo protein design strategy to swiftly engineer decoys for neutralizing pathogens that exploit extracellular host proteins to infect the cell. Our pipeline allowed the design, validation, and optimization of de novo hACE2 decoys to neutralize SARS-CoV-2. The best decoy, CTC-445.2, binds with low nanomolar affinity and high specificity to the RBD of the spike protein. Cryo-EM shows that the design is accurate and can simultaneously bind to all three RBDs of a single spike protein. Because the decoy replicates the spike protein target interface in hACE2, it is intrinsically resilient to viral mutational escape. A bivalent decoy, CTC-445.2d, shows ~10-fold improvement in binding. CTC-445.2d potently neutralizes SARS-CoV-2 infection of cells in vitro and a single intranasal prophylactic dose of decoy protected Syrian hamsters from a subsequent lethal SARS-CoV-2 challenge.

DOI: 10.1126/science.abe0075

Source: https://science.sciencemag.org/content/early/2020/11/04/science.abe0075