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

Chem Commun (Camb). 2022 Feb 3;58(11):1804-1807. doi: 10.1039/d1cc06301d.

Authors

Yan-Ni Zhang¹, Yuwei Zhang², Shan Su³, Han-Ying Zhu¹, Wei Xu³, Lu Wang², Meng Wu¹, Kai Chen¹, Fei-Qiang Yu¹, Tong-Kuai Xi¹, Qin Zhou¹, You-Hua Xie³, Ximing Qin¹, Honghua Ge¹, Lu Lu³, Jie Qing², Ge-Min Fang¹

Affiliations

¹ Department of Health Sciences, Institutes of Physical Science and Information Technology, Anhui University, Hefei 230601, P. R. China. fanggm@ahu.edu.cn.
² National Traditional Chinese Medicine Clinical Research Base, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, 646000, P. R. China. qing282420@163.com.
³ 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. lul@fudan.edu.cn.

PMID: 35040445
DOI: 10.1039/d1cc06301d

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.

MeSH terms

Amino Acid Sequence
Angiotensin-Converting Enzyme 2 / chemistry
Antiviral Agents / chemical synthesis
Antiviral Agents / metabolism
Antiviral Agents / pharmacology*
Cell Line, Tumor
Humans
Microbial Sensitivity Tests
Peptide Fragments / chemical synthesis
Peptide Fragments / metabolism
Peptide Fragments / pharmacology*
Peptidomimetics / chemical synthesis
Peptidomimetics / metabolism
Peptidomimetics / pharmacology*
Protein Binding
Protein Domains
SARS-CoV-2 / drug effects*
Spike Glycoprotein, Coronavirus / chemistry
Spike Glycoprotein, Coronavirus / metabolism

Substances

Antiviral Agents
Peptide Fragments
Peptidomimetics
Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2
ACE2 protein, human
Angiotensin-Converting Enzyme 2