Volume 31, No 1, Jan 2021

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 31 Issue 1, January 2021: 98-100

LETTERS TO THE EDITOR

Engineered trimeric ACE2 binds viral spike protein and locks it in “Three-up” conformation to potently inhibit SARS-CoV-2 infection

Liang Guo^1,2,3 , Wenwen Bi^1,2,3 , Xinling Wang⁴ , Wei Xu⁴ , Renhong Yan^1,2,3 , Yuanyuan Zhang^1,2,3 , Kai Zhao^1,2,3 , Yaning Li^1,2,3 , Mingfeng Zhang^1,2,3 , Xia Cai⁴ , Shibo Jiang⁴ , Youhua Xie⁴ , Qiang Zhou^1,2,3,* , Lu Lu^4,* , Bobo Dang^1,2,3,*

¹Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang 310024, China
²Center for Infectious Disease Research, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang 310024, China
³Institute of Biology, Westlake Institute for Advanced Study, Hangzhou, Zhejiang 310024, China
⁴Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences and Biosafety Level 3 Laboratory, Fudan University, Shanghai, 200032, China
These authors contributed equally: Liang Guo, Wenwen Bi, Xinling Wang, Wei Xu, Renhong Yan, Yuanyuan Zhang These authors jointly supervised this work: Youhua Xie, Qiang Zhou, Lu Lu, Bobo Dang Correspondence: Qiang Zhou(zhouqiang@westlake.edu.cn)Lu Lu(lul@fudan.edu.cn)Bobo Dang(dangbobo@westlake.edu.cn)

Dear Editor,

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in a severe global pandemic. Following SARS-CoV, SARS-CoV-2 is yet another emergent beta-coronavirus threatening human health.1 However, seventeen years after the SARS pandemic, no targeted vaccines or therapeutics have been approved for SARS, while some of them might have held promise for treating COVID-19. Many neutralizing antibodies against SARS-CoV-2 are currently being developed. However, RNA viruses are known to have high mutation rates. Many SARS-CoV-2 mutations have already been identified such as D614G,2 and these resultant mutation strains might escape the effects of the current SARS-CoV-2 neutralizing antibodies. The appearance of COVID-19 after SARS indicates the likely emergence of other coronavirus pandemics in the future. Thus, therapeutics broadly effective against SARS-CoV-2 and mutants, even other SARS-CoV-2-related coronaviruses (SARSr-CoVs), are highly desirable. Both SARS-CoV-2 and SARS-CoV bind ACE2 for cell entry, suggesting a general use of ACE2 by SARS-CoV-2 mutants and future related coronaviruses. Therefore, proteins engineered based on wild-type ACE2 might exhibit the best broad neutralizing activity and avoid the mutational escape.

https://doi.org/10.1038/s41422-020-00438-w

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