2. Academic Validation
  3. Development of an ultrahigh affinity, trimeric ACE2 biologic as a universal SARS-CoV-2 antagonist

Development of an ultrahigh affinity, trimeric ACE2 biologic as a universal SARS-CoV-2 antagonist

  • Commun Biol. 2025 Oct 6;8(1):1428. doi: 10.1038/s42003-025-08819-w.
Juliet Gonzales # 1 2,  Tynan Young # 2,  Hyeran Choi 2,  Miso Park 2,  Yead Jewel 2,  Chengcheng Fan 3,  Rahul Purohit 2,  Pamela J Bjorkman 3,  John C Williams 4 5
Affiliations

Affiliations

  • 1 Irell and Manella Graduate School of Biological Sciences, Beckman Research Institute, City of Hope, Duarte, CA, USA.
  • 2 Department of Cancer Biology and Molecular Medicine, Beckman Research Institute, City of Hope, Duarte, CA, USA.
  • 3 Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
  • 4 Irell and Manella Graduate School of Biological Sciences, Beckman Research Institute, City of Hope, Duarte, CA, USA. jcwilliams@coh.org.
  • 5 Department of Cancer Biology and Molecular Medicine, Beckman Research Institute, City of Hope, Duarte, CA, USA. jcwilliams@coh.org.
  • # Contributed equally.
PMID: 41053501 DOI: 10.1038/s42003-025-08819-w
Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the COVID-19 pandemic, utilizes membrane-bound, angiotensin-converting enzyme II (ACE2) for internalization and Infection. We describe the development of a biologic that takes advantage of the proximity of the N-terminus of bound ACE2 to the three-fold symmetry axis of the spike protein to create an ultrapotent, trivalent ACE2 entry antagonist. Distinct disulfide bonds were added to enhance serum stability and a single point mutation was introduced to eliminate enzymatic activity. Through surface plasmon resonance, pseudovirus neutralization assays, and single-particle cryo-electron microscopy, we show this antagonist binds to and inhibits SARS-CoV-2 variants. We further show the antagonist binds to and inhibits a 2003 SARS-CoV-1 strain. Collectively, structural insight has allowed us to design a universal trivalent antagonist against all variants of SARS-CoV-2 tested, suggesting it will be active against the emergence of future mutants.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z