Engineered Human Cathelicidin Antimicrobial Peptides Inhibit Ebola Virus Infection.
Yu. Yangsheng Y; Cooper. Christopher L CL; Wang. Guangshun G; Morwitzer. M Jane MJ; Kota. Krishna K; Tran. Julie P JP; Bradfute. Steven B SB; Liu. Yan Y; Shao. Jiayu J; Zhang. Amanda K AK; Luo. Lindsey G LG; Reid. St Patrick SP; Hinrichs. Steven H SH; Su. Kaihong K
Key Findings
- LL-37 and engineered LL-37 peptides block infection by Ebola virus‑like particles and real Ebola virus.
- The peptides act during the virus’s entry step by preventing cathepsin B from processing the viral glycoprotein.
- Engineered versions that contain D‑amino acids are especially potent, likely because they are less vulnerable to enzymatic degradation.
Practical Outcomes
- These results are mainly of interest for drug development against Ebola and do not provide a ready‑to‑use protocol for health‑optimizing individuals. The findings suggest that peptide engineering can improve antiviral potency, but more research and safety testing are needed before any self‑administration could be considered.
Summary
Scientists found that the natural peptide LL-37 and specially engineered versions can stop Ebola virus from infecting cells in lab experiments. The engineered peptides work better because they resist being broken down inside cells.
Abstract
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.
Study Information
pubmed
2020
2020-03-22T00:00:00.000Z
10.1016/j.isci.2020.100999
42
76