Neutralizing SARS-CoV-2 by dimeric side chain-to-side chain cross-linked ACE2 peptide mimetics

Yan-Ni Zhang; Yuwei Zhang; Shan Su; Han-Ying Zhu; Wei Xu; Lu Wang; Meng Wu; Kai Chen; Fei-Qiang Yu; Tong-Kuai Xi; Qin Zhou; You-Hua Xie; Ximing Qin; Honghua Ge; Lu Lu; Jie Qing; Ge-Min Fang

doi:10.1039/D1CC06301D

Neutralizing SARS-CoV-2 by dimeric side chain-to-side chain cross-linked ACE2 peptide mimetics†

Yan-Ni Zhang,‡^a Yuwei Zhang,‡^b Shan Su,‡^c Han-Ying Zhu,‡^a Wei Xu,^c Lu Wang,^b Meng Wu,^a Kai Chen,^a Fei-Qiang Yu,^a Tong-Kuai Xi,^a Qin Zhou,^a You-Hua Xie,^c Ximing Qin,^a Honghua Ge,^a Lu Lu,*^c Jie Qing*^b and Ge-Min Fang

*^a

Author affiliations

* Corresponding authors

^a Department of Health Sciences, Institutes of Physical Science and Information Technology, Anhui University, Hefei 230601, P. R. China
E-mail: fanggm@ahu.edu.cn

^b National Traditional Chinese Medicine Clinical Research Base, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, P. R. China
E-mail: qing282420@163.com

^c Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences and Biosafety Level 3 Laboratory, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200032, P. R. China
E-mail: lul@fudan.edu.cn

Abstract

We present the finding of a dimeric ACE2 peptide mimetic designed through side chain cross-linking and covalent dimerization. It has a binding affinity of 16 nM for the SARS-CoV-2 spike RBD, and effectively inhibits the SARS-CoV-2 pseudovirus in Huh7-hACE2 cells with an IC₅₀ of 190 nM and neutralizes the authentic SARS-CoV-2 in Caco2 cells with an IC₅₀ of 2.4 μM. Our study should provide a new insight for the optimization of peptide-based anti-SARS-CoV-2 inhibitors.

Chemical Communications

Neutralizing SARS-CoV-2 by dimeric side chain-to-side chain cross-linked ACE2 peptide mimetics†

Abstract

Supplementary files

Article information

Download Citation

Permissions

Neutralizing SARS-CoV-2 by dimeric side chain-to-side chain cross-linked ACE2 peptide mimetics

Social activity

Search articles by author

Spotlight

Advertisements