Figure 1

Schematic diagram showing the replication cycle of Ebola virus (EBOV): Upon receptor binding of EBOV GP₁ with host TIM-1 receptor, EBOV is internalized into endosome via macropinocytosis. Within the acidified endosome compartment of the host cell, under the action of the low pH-dependent cellular proteases cathepsins, the receptor binding site of GP₁ to cholesterol transporter Niemann-Pick C1 (NPC1) is exposed. This results in conformational change in GP₂ , leading to complete fusion of the viral and host endosomal membranes in the late endosome and the release of viral RNA and its associated proteins into the host cell cytoplasm. EBOV then hijacks transcription and translation for robust genome replication and viral protein production under the action of ribonucleoprotein polymerase complex (RNP polymerase). The accumulation of GP_1,2 in the endoplasmic reticulum leads to endoplasmic reticulum overload response (ER-overload) which, in turn, induces cytokine dysregulation via the activation of nuclear factor kappa B (NFκB) through the production of reactive oxygen species (ROS). New virions are released through ATP-dependent budding and egress from host cell membrane. Currently available therapeutic agents that target the different steps of the EBOV life cycle are described in Table 1.