Engineered Human Cathelicidin Antimicrobial Peptides Inhibit Ebola Virus Infection

Engineered Human Cathelicidin Antimicrobial Peptides Inhibit Ebola Virus Infection

Summary: The 2014–2016 West Africa Ebola virus (EBOV) outbreak coupled with the most recent outbreaks in Central Africa underscore the need to develop effective treatment strategies against EBOV. Although several therapeutic options have shown great potential, developing a wider breadth of counterme...

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Main Authors: Yangsheng Yu, Christopher L. Cooper, Guangshun Wang, M. Jane Morwitzer, Krishna Kota, Julie P. Tran, Steven B. Bradfute, Yan Liu, Jiayu Shao, Amanda K. Zhang, Lindsey G. Luo, St. Patrick Reid, Steven H. Hinrichs, Kaihong Su
Format: Article
Language:English
Published: Elsevier 2020-04-01
Series:iScience
Online Access:http://www.sciencedirect.com/science/article/pii/S2589004220301838
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spelling doaj-7c1edf2881374d54a28d8ed4d8a6d8492020-11-25T02:02:51ZengElsevieriScience2589-00422020-04-01234Engineered Human Cathelicidin Antimicrobial Peptides Inhibit Ebola Virus InfectionYangsheng Yu0Christopher L. Cooper1Guangshun Wang2M. Jane Morwitzer3Krishna Kota4Julie P. Tran5Steven B. Bradfute6Yan Liu7Jiayu Shao8Amanda K. Zhang9Lindsey G. Luo10St. Patrick Reid11Steven H. Hinrichs12Kaihong Su13Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USAMolecular and Translational Sciences, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD 21702, USADepartment of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USADepartment of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USAMolecular and Translational Sciences, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD 21702, USAMolecular and Translational Sciences, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD 21702, USAInternal Medicine, Center for Global Health, University of New Mexico, Albuquerque, NM 87131, USADepartment of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USADepartment of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USADepartment of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USADepartment of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USADepartment of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USADepartment of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USADepartment of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA; Corresponding authorSummary: The 2014–2016 West Africa Ebola virus (EBOV) outbreak coupled with the most recent outbreaks in Central Africa underscore the need to develop effective treatment strategies against EBOV. Although several therapeutic options have shown great potential, developing a wider breadth of countermeasures would increase our efforts to combat the highly lethal EBOV. Here we show that human cathelicidin antimicrobial peptide (AMP) LL-37 and engineered LL-37 AMPs inhibit the infection of recombinant virus pseudotyped with EBOV glycoprotein (GP) and the wild-type EBOV. These AMPs target EBOV infection at the endosomal cell-entry step by impairing cathepsin B-mediated processing of EBOV GP. Furthermore, two engineered AMPs containing D-amino acids are particularly potent in blocking EBOV infection in comparison with other AMPs, most likely owing to their resistance to intracellular enzymatic degradation. Our results identify AMPs as a novel class of anti-EBOV therapeutics and demonstrate the feasibility of engineering AMPs for improved therapeutic efficacy. : Drugs; Molecular Biology; Viral Microbiology Subject Areas: Drugs, Molecular Biology, Viral Microbiologyhttp://www.sciencedirect.com/science/article/pii/S2589004220301838
collection DOAJ
language English
format Article
sources DOAJ
author Yangsheng Yu
Christopher L. Cooper
Guangshun Wang
M. Jane Morwitzer
Krishna Kota
Julie P. Tran
Steven B. Bradfute
Yan Liu
Jiayu Shao
Amanda K. Zhang
Lindsey G. Luo
St. Patrick Reid
Steven H. Hinrichs
Kaihong Su
spellingShingle Yangsheng Yu
Christopher L. Cooper
Guangshun Wang
M. Jane Morwitzer
Krishna Kota
Julie P. Tran
Steven B. Bradfute
Yan Liu
Jiayu Shao
Amanda K. Zhang
Lindsey G. Luo
St. Patrick Reid
Steven H. Hinrichs
Kaihong Su
Engineered Human Cathelicidin Antimicrobial Peptides Inhibit Ebola Virus Infection
iScience
author_facet Yangsheng Yu
Christopher L. Cooper
Guangshun Wang
M. Jane Morwitzer
Krishna Kota
Julie P. Tran
Steven B. Bradfute
Yan Liu
Jiayu Shao
Amanda K. Zhang
Lindsey G. Luo
St. Patrick Reid
Steven H. Hinrichs
Kaihong Su
author_sort Yangsheng Yu
title Engineered Human Cathelicidin Antimicrobial Peptides Inhibit Ebola Virus Infection
title_short Engineered Human Cathelicidin Antimicrobial Peptides Inhibit Ebola Virus Infection
title_full Engineered Human Cathelicidin Antimicrobial Peptides Inhibit Ebola Virus Infection
title_fullStr Engineered Human Cathelicidin Antimicrobial Peptides Inhibit Ebola Virus Infection
title_full_unstemmed Engineered Human Cathelicidin Antimicrobial Peptides Inhibit Ebola Virus Infection
title_sort engineered human cathelicidin antimicrobial peptides inhibit ebola virus infection
publisher Elsevier
series iScience
issn 2589-0042
publishDate 2020-04-01
description Summary: The 2014–2016 West Africa Ebola virus (EBOV) outbreak coupled with the most recent outbreaks in Central Africa underscore the need to develop effective treatment strategies against EBOV. Although several therapeutic options have shown great potential, developing a wider breadth of countermeasures would increase our efforts to combat the highly lethal EBOV. Here we show that human cathelicidin antimicrobial peptide (AMP) LL-37 and engineered LL-37 AMPs inhibit the infection of recombinant virus pseudotyped with EBOV glycoprotein (GP) and the wild-type EBOV. These AMPs target EBOV infection at the endosomal cell-entry step by impairing cathepsin B-mediated processing of EBOV GP. Furthermore, two engineered AMPs containing D-amino acids are particularly potent in blocking EBOV infection in comparison with other AMPs, most likely owing to their resistance to intracellular enzymatic degradation. Our results identify AMPs as a novel class of anti-EBOV therapeutics and demonstrate the feasibility of engineering AMPs for improved therapeutic efficacy. : Drugs; Molecular Biology; Viral Microbiology Subject Areas: Drugs, Molecular Biology, Viral Microbiology
url http://www.sciencedirect.com/science/article/pii/S2589004220301838
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