Peptide S4 is an entry inhibitor of SARS-CoV-2 infection

• Published in: Virology (New York, N.Y.) N.Y.), 2024-09, Vol.597, p.110149, Article 110149
• Main Authors: Liang, Zhiyu, Wang, Jiamei, Zhang, Huan, Gao, Lixia, Xu, Jun, Li, Peiran, Yang, Jie, Fu, Xinting, Duan, Han, Liu, Jiayan, Liu, Tiancai, Ma, Weifeng, Wu, Kun
• Format: Article
• Language: English
• Subjects: Angiotensin-converting enzyme 2; Angiotensin-Converting Enzyme 2 - metabolism; Animals; Antiviral Agents - pharmacology; Chlorocebus aethiops; Coronavirus NL63, Human - drug effects; Coronavirus NL63, Human - physiology; COVID-19 - virology; COVID-19 Drug Treatment; Entry inhibitor; Humans; Peptides - pharmacology; Protein Binding; S protein; SARS-CoV-2; SARS-CoV-2 - drug effects; SARS-CoV-2 - physiology; Spike Glycoprotein, Coronavirus - antagonists & inhibitors; Spike Glycoprotein, Coronavirus - metabolism; Virus Internalization - drug effects
• ISSN: 0042-6822; 1096-0341; 1096-0341
• DOI: 10.1016/j.virol.2024.110149

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a significant socioeconomic burden, and combating COVID-19 is imperative. Blocking the SARS-CoV-2 RBD–ACE2 interaction is a promising therapeutic approach for viral infections, as SARS-CoV-2 binds to the ACE2 receptors of host cells via the RBD of spike proteins to infiltrate these cells. We used computer-aided drug design technology and cellular experiments to screen for peptide S4 with high affinity and specificity for the human ACE2 receptor through structural analysis of SARS-CoV-2 and ACE2 interactions. Cellular experiments revealed that peptide S4 effectively inhibited SARS-CoV-2 and HCoV-NL63 viruses from infecting host cells and was safe for cells at effective concentrations. Based on these findings, peptide S4 may be a potential pharmaceutical agent for clinical application in the treatment of the ongoing SARS-CoV-2 pandemic. •We use computer-aided drug design and cellular tests to screen peptide inhibitors.•Peptide S4 is a potent coronavirus entry inhibitor.•Peptide S4 inhibits the ACE2 receptor and competes with the virus for binding.