Therapeutics: Ebolavirus glycoprotein; Niemann-Pick disease type C1 (NPC1)

Mouse and guinea pig studies identified a mAb that could help treat Ebola caused by the Ebola and Sudan species of Ebolavirus. A previously identified macaque-derived mAb bound Ebolavirus glycoprotein from multiple Ebola species with EC50 values of 0.017-0.05 µg/mL. In a mammalian cell-based binding assay, the mAb inhibited binding between Ebolavirus glycoprotein from Ebola virus and Sudan virus and the glycoprotein's host cell receptor NPC1 with EC50 values of 3.4 and 4.3 µg/mL, respectively. In a mouse model of Ebola, the anti-glycoprotein mAb decreased weight loss and increased survival compared with vehicle. In a mouse model of the Sudan virus infection, the mAb increased survival compared with no treatment. In guinea pig models of Ebola virus or Sudan virus infection, the anti-glycoprotein mAb or a version of Zmapp that substituted a Zmapp mAb with the anti-glycoprotein mAb increased survival compared with vehicle. Next steps include testing the mAb alone and in combination with other anti-Ebola mAbs in non-human primate models of Ebolavirus infection...