Fig. 2 Possible mechanisms of endolysosomal pH-modulation-mediated effects on the structure and function of endolysosomal vesicles with potential consequences for viral fusion, trafficking and shedding. (A) Drugs affecting activity of vesicular acidification mechanisms neutralize endolysosomal compartments. The illustration shows the general structure of a proton pump inhibitor; this might neutralize endolysosomal compartments through inhibition of vacuolar-type H+-ATPase (V-ATPase). (B) Weakly basic and lipophilic properties of lysosomotropic compounds enable them to diffuse passively through the endosomal membrane and undergo protonation-based trapping and subsequent neutralization of acidic vesicles. (C) The acidic environment enables conformational changes that activate viral fusion proteins. Moreover, H+ interacts with the viral matrix and activates mechanisms implicated in later stages of viral fusion and/or uncoating. (D) Acidic pH of endolysosomal compartments activates proteases involved with viral fusion processes. (E) The acidic luminal environment activates endolysosomal trafficking regulatory proteins [56].