Yu Yangsheng, Cooper Christopher L, Wang Guangshun, Morwitzer M Jane, Kota Krishna, Tran Julie P, Bradfute Steven B, Liu Yan, Shao Jiayu, Zhang Amanda K, Luo Lindsey G, Reid St Patrick, Hinrichs Steven H, Su Kaihong
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Molecular and Translational Sciences, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD 21702, USA.
iScience. 2020 Apr 24;23(4):100999. doi: 10.1016/j.isci.2020.100999. Epub 2020 Mar 22.
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.
2014 - 2016年西非埃博拉病毒（EBOV）疫情，再加上最近在中非爆发的疫情，凸显了开发针对EBOV的有效治疗策略的必要性。尽管几种治疗方案已显示出巨大潜力，但开发更广泛的应对措施将加大我们对抗高致死性EBOV的力度。在此我们表明，人组织蛋白酶抗菌肽（AMP）LL - 37以及工程化的LL - 37 AMP可抑制用EBOV糖蛋白（GP）假型化的重组病毒和野生型EBOV的感染。这些AMP通过损害组织蛋白酶B介导的EBOV GP加工过程，在内体细胞进入步骤靶向EBOV感染。此外，与其他AMP相比，两种含有D - 氨基酸的工程化AMP在阻断EBOV感染方面特别有效，这很可能是由于它们对细胞内酶降解具有抗性。我们的结果确定AMP为一类新型抗EBOV治疗剂，并证明了对AMP进行工程改造以提高治疗效果的可行性。
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