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  Új Válasz 2020-11-04 22:00:44 #54371

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  [Azithromycin and ambroxol as potential pharmacotherapy for SARS-CoV-2]

  "3.2. Ambroxol

  Ambroxol is a mucolytic agent used in the treatment of respiratory diseases. Ambroxol is a basic (pKa = 9.01) cationic drug with lipophilic properties (logP = 2.9), enabling it to act as a lysosomotropic agent. In addition, ambroxol exhibits a novel mechanism by accumulating in lamellar bodies and acting as a lysosomal secretagogue. This may also play a role in its use for lysosomal storage diseases [29]. Moreover, ambroxol can induce autophagy, which may have a role in fighting SARS-CoV-2 [30].

  The main effect of ambroxol is on mucus regulation, however a wide range of pharmacological effects of ambroxol have been confirmed, including anti-inflammatory, reduction of arachidonic acid metabolites and pro-inflammatory cytokines, and antioxidant properties. In addition, ambroxol aids in the enhancement of local defence molecules involved in respiratory viral replication [31].

  It has been reported that SARS-CoV-2 binds to alveolar type 2 (AT2) epithelial cells where ACE2 receptors are highly expressed [32]. AT2 cells are responsible for the production of surfactant. One mechanism of action of ambroxol is to act specifically on AT2 cells and to stimulate the release of surfactant, which aids in preventing influenza virus multiplication and in maintaining alveolar function and preventing alveolar collapse [33].

  The antiviral effect of ambroxol may be due to upregulation of natural inhibitors of proteases that represents a potential therapeutic approach to suppress viral airway replication. A study conducted on rats showed that treatment of animals with ambroxol prior to infection with influenza A virus led to a substantial suppression of virus multiplication as well as improved survival [33].

  Despite the presence of registered clinical trials on the prodrug bromhexine, the precursor of ambroxol (https://clinicaltrials.gov/ct2/show/NCT04355026), there is no registered clinical trial on ambroxol in COVID-19. Interestingly, one Chinese study mentioned the use of ambroxol as symptomatic treatment of cough in children with COVID-19 [34]. In addition, there are three case reports mentioning the use of ambroxol as symptomatic treatment for relief of phlegm [35,36].

  As mentioned previously, there is evidence that SARS-CoV-2 may invade host cells through binding to ACE2 receptors present in the nasal cavity. Accordingly, inhaler administration of ambroxol may represent an efficient delivery method of ambroxol to the target site with fewer systemic side effects. Notably, ambroxol inhalation has been approved as an efficient and convenient therapy for other respiratory diseases [37] and is available in some countries as an ampule for inhalation."

  Összefoglalva:

  Az ambroxol lizoszomotrop tulajdonságokkal rendelkezik, így ez a gyógyszer blokkolja a virus fertőzőképességét. Ezenkívül gyulladáscsökkentő hatásuk van, míg az ambroxol további bevált vírusellenes hatással és felületaktív stimuláló hatással bír, amelyek hozzájárulhatnak a vírus elleni veleszületett immunmechanizmushoz.
  
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