Engineered Human Cathelicidin Antimicrobial Peptides Inhibit Ebola Virus Infection

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

iScience (Apr 2020)

Engineered Human Cathelicidin Antimicrobial Peptides Inhibit Ebola Virus Infection

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

Affiliations

Yangsheng Yu: Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA
Christopher L. Cooper: Molecular and Translational Sciences, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD 21702, USA
Guangshun Wang: Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA
M. Jane Morwitzer: Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA
Krishna Kota: Molecular and Translational Sciences, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD 21702, USA
Julie P. Tran: Molecular and Translational Sciences, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD 21702, USA
Steven B. Bradfute: Internal Medicine, Center for Global Health, University of New Mexico, Albuquerque, NM 87131, USA
Yan Liu: Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA
Jiayu Shao: Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA
Amanda K. Zhang: Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA
Lindsey G. Luo: Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA
St. Patrick Reid: Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA
Steven H. Hinrichs: Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA
Kaihong Su: Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA; Corresponding author

Journal volume & issue: Vol. 23, no. 4

Abstract

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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

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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