From:  Small molecules targeting endolysosomal acidification and signaling in sepsis and severe SARS-CoV-2 infection/COVID-19

Impact of small molecules on inflammatory messengers and growth factors in sepsis and severe SARS-CoV-2 infection/COVID-19

MediatorSepsisCOVID-19Lysosomotropic small molecules
TNFα↑↑/w/oTarget↓
IL-1β↑↑/w/oTarget↓
IL-1RA↑↑n.d.Unknown
IL-2↑w/o-o
IL-6↑↑Target↓↓
IL-7↑↑Target↓
IL-8↑↓/↑n.d.Unknown
IL-10↑↑Target°↑°
IL-15↑↑-o
IL-17Aw/o↑/w/o-o
IFN-γ↓/↑↑n.d.Unknown
TGF-β↓/w/o↑-o
MCP-1/CCL2↑↑Target↓**
CCL4↑/w/ow/oTarget↓↓
CCL5↑↑/w/o-o
CCL22-↑-o
PTX3↑↑Target↓↓
CXCL2--Target↓↓
CXCL3--Target↓↓
CXCL10↑↑Target↓↓
C3/C3aR↓↑/w/oTarget C3aRo/↓+
C4↓w/on.d.Unknown
C5b-C9↑↑n.d.Unknown
C5a/C5aR↑↑Target C5aRo/↓+
GM-CSF↓/↑↓/↑n.d.Unknown
ICAM-1↑↑Target↓
VCAM1↑↑Target↓#
PTGS2--Target↓#
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Messenger/growth factor release depends on disease severity in sepsis [47–62] and severe SARS-CoV-2 infection/COVID-19 [3–9, 63–65]: increased (↑), decreased (↓), without (relevant) changes (w/o), (yet) unknown (-). Targets of lysosomotropic small molecules, inhibitors of endolysosomal acidification, and disruptors of lysosomal proton gradients are indicated as: target (Target), no target (-), or not determined (n.d.). Effects on gene expression [messenger RNA (mRNA)] in LPS stimulated human monomac 6 cells are indicated as: increased (↑), decreased (↓), no effect (o). Reference compound for small lysosomotropic molecules: NB 06 [22], plus literature data of fluvoxamine [66]#, amitriptyline [67]°, and ambroxol [68]**. + determined as C5 mRNA; IFN-γ: interferon-γ; TGF-β: transforming growth factor-β; MCP-1: monocyte chemoattractant protein-1; CCL2: C-C motif chemokine ligand 2; CXCL2: CXC motif chemokine ligand 2; ICAM-1: intercellular adhesion molecule-1; VCAM1: vascular cell adhesion molecule 1; PTGS2: prostaglandin-endoperoxide synthase 2