Effects of the glycosylation of the receptor binding domain (RBD dimer)-based Covid-19 vaccine (ZF2001) on its humoral immunogenicity and immunoreactivity

Affiliations

• Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, 132 East Outer Ring Road, Guangzhou 511400, China.
• College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
• Department of Orthopaedics and Traumatology, Zhongshan Hospital of Traditional Chinese Medicine, Zhongshan 528400, China.
• State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
• School of Life Sciences, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences & Research Unit of Peptide Science, 2019RU066, Lanzhou University, 199 West Donggang Rd, Lanzhou 730000, China.

PMID: 37279405 DOI: 10.1021/acs.jmedchem.3c005

Abstract

Kidney fibrosis is a serious consequence of chronic kidney disease (CKD), and currently, there is no effective pharmacological treatment available. Cellular communication network-2 (CCN2/CTGF) is an extracellular matrix (ECM) protein that regulates the fibrotic process by activating the epidermal growth factor receptor (EGFR) signaling pathway. We herein present the discovery and structure-activity relationship study of novel peptides targeting CCN2 to develop potent and stable specific inhibitors of the CCN2/EGFR interaction. Remarkably, the 7-mer cyclic peptideOK2exhibited potent activities to inhibit CCN2/EGFR-induced STAT3 phosphorylation and cellular ECM protein synthesis. Subsequent in vivo studies demonstrated thatOK2significantly alleviated renal fibrosis in a unilateral ureteral obstruction (UUO) mouse model. Moreover, this study first revealed that the peptide candidate could efficiently block CCN2/EGFR interaction through binding to the CT domain of CCN2, providing a new alternative strategy for peptide-based targeting of CCN2 and modulating CCN2/EGFR-mediated biological functions in kidney fibrosis.