ambroxol is an approved drug
Compound class:
Synthetic organic
Comment: Ambroxol stimulates the synthesis and release of surfactant in the respiratory tract and acts as a mucoactive/expectorant drug. This action appears to be associated with ambroxol's regulation of glucosylceramide levels, via modulation of non-lysosomal glucosylceramidase (GCase) beta 2 (GBA2; Q9HCG7). Ambroxol is reported to act as a small molecule chaperone for GCase proteins that can increase the stability and function of mutant and wild-type GCases in in vitro and in vivo models [4-5,7-8,17], and in clinical trial subjects [12,18]. Ambroxol binds to nascent GCase proteins (at the enzyme active site) within the endoplasmic reticulum, and this action facilitates transport to the lysosome [1,4]. The acidic lysosomal environment provokes ambroxol disassociation, leaving the enzyme free to function normally.
SARS-CoV-2 and COVID-19: Evidence presented in a preprint suggests that ambroxol (and its prodrug bromhexine) directly disrupts the protein-protein interaction between the SARS-CoV-2 spike protein and ACE2 [14]. This action is reported to inhibit the cytopathic effects induced by SARS-CoV-2 infection in vitro, which is suggestive of potential prophylactic and/or therapeutic use of these drugs against COVID-19. |
|
|||||||||||||||||||||||||||||||||||
| Bioactivity Comments |
| Ambroxol behaves as an inhibitory GCase chaperone at neutral pH, so within acellular human CSF it produces an inhibitory effect on GCase activity [11]. In contrast, within cells and their acidic lysosomes ambroxol increases intracellular GCase activity by elevating the enzyme mass that reaches the lysosomes [8-9]. |
| Selectivity at enzymes | ||||||||||||||||||||||||||||||||||
| Key to terms and symbols | Click column headers to sort | |||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
