Engineered Human Cathelicidin Antimicrobial Peptides Inhibit Ebola Virus Infection

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

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.