Affordable Access

deepdyve-link
Publisher Website

Human Cathelicidin Inhibits SARS-CoV-2 Infection: Killing Two Birds with One Stone.

Authors
  • Wang, Cheng1
  • Wang, Shaobo2
  • Li, Daixi3
  • Chen, Peiqin3
  • Han, Songling1
  • Zhao, Gaomei1
  • Chen, Yin1
  • Zhao, Jianqi1
  • Xiong, Jiachuan2
  • Qiu, Jingfei4
  • Wei, Dong-Qing4, 5
  • Zhao, Jinghong2
  • Wang, Junping1
  • 1 State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury of PLA, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, China. , (China)
  • 2 Department of Nephrology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China. , (China)
  • 3 Institute of Biothermal Science and Technology, University of Shanghai for Science and Technology, Shanghai 20093, China. , (China)
  • 4 AI Research Center, Peng Cheng Laboratory, Shenzhen, Guangdong 518055, China. , (China)
  • 5 State Key Laboratory of Microbial Metabolism, Shanghai-Islamabad-Belgrade Joint Innovation Center on Antibacterial Resistances, Joint Laboratory of International Cooperation in Metabolic and Developmental Sciences, Ministry of Education and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200030, China. , (China)
Type
Published Article
Journal
ACS Infectious Diseases
Publisher
American Chemical Society
Publication Date
Jun 11, 2021
Volume
7
Issue
6
Pages
1545–1554
Identifiers
DOI: 10.1021/acsinfecdis.1c00096
PMID: 33849267
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

SARS-CoV-2 infection begins with the association of its spike 1 (S1) protein with host angiotensin-converting enzyme-2 (ACE2). Targeting the interaction between S1 and ACE2 is a practical strategy against SARS-CoV-2 infection. Herein, we show encouraging results indicating that human cathelicidin LL37 can simultaneously block viral S1 and cloak ACE2. LL37 binds to the receptor-binding domain (RBD) of S1 with high affinity (11.2 nM) and decreases subsequent recruitment of ACE2. Owing to the RBD blockade, LL37 inhibits SARS-CoV-2 S pseudovirion infection, with a half-maximal inhibitory concentration of 4.74 μg/mL. Interestingly, LL37 also binds to ACE2 with an affinity of 25.5 nM and cloaks the ligand-binding domain (LBD), thereby decreasing S1 adherence and protecting cells against pseudovirion infection in vitro. Intranasal administration of LL37 to C57 mice infected with adenovirus expressing human ACE2 either before or after pseudovirion invasion decreased lung infection. The study identified a versatile antimicrobial peptide in humans as an inhibitor of SARS-CoV-2 attachment using dual mechanisms, thus providing a potential candidate for coronavirus disease 2019 (COVID-19) prevention and treatment.

Report this publication

Statistics

Seen <100 times