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

Zhiyu Liang; Jiamei Wang; Huan Zhang; Lixia Gao; Jun Xu; Peiran Li; Jie Yang; Xinting Fu; Han Duan; Jiayan Liu; Tiancai Liu; Weifeng Ma; Kun Wu

doi:10.1016/j.virol.2024.110149

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

Virology. 2024 Sep:597:110149. doi: 10.1016/j.virol.2024.110149. Epub 2024 Jun 19.

Authors

Zhiyu Liang¹, Jiamei Wang², Huan Zhang³, Lixia Gao², Jun Xu⁴, Peiran Li², Jie Yang², Xinting Fu², Han Duan², Jiayan Liu⁵, Tiancai Liu⁶, Weifeng Ma⁷, Kun Wu⁸

Affiliations

¹ Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, 510515, China; Department of Microbiology, School of Public Health, Southern Medical University, Guangzhou, 510515, China.
² Department of Microbiology, School of Public Health, Southern Medical University, Guangzhou, 510515, China.
³ Guangdong Center for Disease Control and Prevention, Guangdong, China.
⁴ College of Pharmacy, Jinan University, Guangzhou, China.
⁵ Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, 510515, China; Institute of Antibody Engineering, School of Laboratory Medicine & Biotechnology, Southern Medical University, Guangzhou, China.
⁶ Institute of Antibody Engineering, School of Laboratory Medicine & Biotechnology, Southern Medical University, Guangzhou, China.
⁷ Department of Microbiology, School of Public Health, Southern Medical University, Guangzhou, 510515, China. Electronic address: pinger@smu.edu.cn.
⁸ Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, 510515, China. Electronic address: wksmu@163.com.

PMID: 38917689
DOI: 10.1016/j.virol.2024.110149

Abstract

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.

Keywords: Angiotensin-converting enzyme 2; Entry inhibitor; S protein; SARS-CoV-2.

MeSH terms

Angiotensin-Converting Enzyme 2* / metabolism
Animals
Antiviral Agents* / pharmacology
COVID-19 / virology
COVID-19 Drug Treatment
Chlorocebus aethiops
Coronavirus NL63, Human / drug effects
Coronavirus NL63, Human / physiology
Humans
Peptides* / pharmacology
Protein Binding
SARS-CoV-2* / drug effects
SARS-CoV-2* / physiology
Spike Glycoprotein, Coronavirus* / antagonists & inhibitors
Spike Glycoprotein, Coronavirus* / metabolism
Virus Internalization* / drug effects

Substances

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