Decoy peptides effectively inhibit the binding of SARS-CoV-2 to ACE2 on oral epithelial cells

Lai-Keng Loi; Cheng-Chieh Yang; Yu-Cheng Lin; Yee-Fun Su; Yi-Chen Juan; Yi-Hsin Chen; Hsiu-Chuan Chang

doi:10.1016/j.heliyon.2023.e22614

Decoy peptides effectively inhibit the binding of SARS-CoV-2 to ACE2 on oral epithelial cells

Heliyon. 2023 Nov 20;9(12):e22614. doi: 10.1016/j.heliyon.2023.e22614. eCollection 2023 Dec.

Authors

Lai-Keng Loi¹, Cheng-Chieh Yang^{1

2}, Yu-Cheng Lin¹, Yee-Fun Su³, Yi-Chen Juan³, Yi-Hsin Chen⁴, Hsiu-Chuan Chang⁴

Affiliations

¹ Department of Dentistry, National Yang Ming Chiao Tung University, Taipei, Taiwan.
² Department of Stomatology, Oral & Maxillofacial Surgery, Taipei Veterans General Hospital, Taipei, Taiwan.
³ iStat Biomedical Co., Ltd, New Taipei City, Taiwan.
⁴ Institute of Oral Biology, National Yang Ming Chiao Tung University, Taipei, Taiwan.

Abstract

The entry of SARS-CoV-2 into host cells involves the interaction between the viral spike protein and the human angiotensin-converting enzyme 2 (ACE2) receptor. Given that the spike protein evolves rapidly to evade host immunity, therapeutics that block ACE2 accessibility, such as spike decoys, could serve as an alternative strategy for attenuating viral infection. Here, we constructed a drug screening platform based on oral epithelial cells to rapidly identify peptides or compounds capable of blocking the spike-ACE2 interaction. We engineered short decoy peptides, 8 to 14 amino acids in length, using the spike protein's receptor-binding motif (RBM) and demonstrated that these peptides can effectively inhibit virus attachment to host cells. Additionally, we discovered that diminazene aceturate (DIZE), an ACE2 activator, similarly inhibited virus binding. Our research thus validates the potential of decoy peptides as a new therapeutic strategy against SARS-CoV-2 infections, opening avenues for further development and study.

Keywords: ACE2; COVID-19; Decoy peptide; Oral epithelial cell; SARS-CoV-2; Spike protein.