Nowadays, COVID-19 represents the most serious inflammatory respiratory disease worldwide. Despite of many proposed therapies, no effective medication has been approved yet. Neutrophils appear to be the key mediator for COVID-19-associated inflammatory immunopathologic, thromboembolic and fibrotic complications. Thus, for any therapeutic agent to be more appropriate, it should greatly block the neutrophilic component of COVID-19. One of the effective therapeutic approaches investigated to reduce neutrophils-associated inflammatory lung diseases with less adverse effects was Roflumilast. Being a highly selective PDE4i, roflumilast acts by enhancing cAMP level, that probably potentiates its anti-inflammatory action via increasing NEP activity. Because activating NEP was previously reported to mitigate several airway inflammatory ailments; this review deeply 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.
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