New putative insights into neprilysin (NEP)-dependent pharmacotherapeutic role of roflumilast in treating COVID-19

• Published in: European journal of pharmacology 2020-12, Vol.889, p.173615-173615, Article 173615
• Main Authors: El Tabaa, Manar Mohammed, El Tabaa, Maram Mohammed
• Format: Article
• Language: English
• Subjects: Aminopyridines - pharmacology; Aminopyridines - therapeutic use; Benzamides - pharmacology; Benzamides - therapeutic use; cAMP; COVID-19; COVID-19 - drug therapy; Cyclopropanes - pharmacology; Cyclopropanes - therapeutic use; Full Length; Humans; IL-6-Induced endothelial dysfunction; Neprilysin; Neprilysin - drug effects; Neutrophil-mediated inflammation; Pandemics; Roflumilast; SARS-CoV-2; TGF-β1-induced pulmonary fibrosis
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2020.173615

Nowadays, coronavirus disease 2019 (COVID-19) represents the most serious inflammatory respiratory disease worldwide. Despite many proposed therapies, no effective medication has yet been approved. Neutrophils appear to be the key mediator for COVID-19-associated inflammatory immunopathologic, thromboembolic and fibrotic complications. Thus, for any therapeutic agent to be effective, it should greatly block the neutrophilic component of COVID-19. One of the effective therapeutic approaches investigated to reduce neutrophil-associated inflammatory lung diseases with few adverse effects was roflumilast. Being a highly selective phosphodiesterase-4 inhibitors (PDE4i), roflumilast acts by enhancing the level of cyclic adenosine monophosphate (cAMP), that probably potentiates its anti-inflammatory action via increasing neprilysin (NEP) activity. Because activating NEP was previously reported to mitigate several airway inflammatory ailments; this review thoroughly discusses the proposed NEP-based therapeutic properties of roflumilast, which may be of great importance in curing COVID-19. However, further clinical studies are required to confirm this strategy and to evaluate its in vivo preventive and therapeutic efficacy against COVID-19. [Display omitted] •NEP-based actions of roflumilast as a novel option for COVID-19 therapy.•Roflumilast may inhibit inflammatory, coagulopathy and fibrotic cascades.