New putative insights into Neprilysin (NEP)-dependent
pharmacotherapeutic role of Roflumilast in treating COVID-19
Abstract
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.