1. Introduction
Coronavirus disease 2019 (COVID-19) is a global infectious illness that
results in a huge number of deaths. For restricting its spread, there is
an urgent need to evok the most effective therapy. (Li et al., 2020b).
Recently, a study hypothesizes
that using the anti-inflammatory phosphodiesterase-4 inhibitor (PDE4i)
for modulating COVID-19 may be beneficial (Bridgewood et al., 2020).
Among PDE4i, roflumilast exhibits the highest potency for targeting and
blunting airway inflammation via enhancing the level of cAMP (Rabe,
2011), which in turn may prolong its anti-inflammatory effect by
activating Neprilysin
(NEP) (Graf et al., 1995). As NEP
is lately supposed to be a new potential target for COVID-19 therapy (El
Tabaa and El Tabaa, 2020), roflumilast-enhanced NEP activity may have a
prominent significance. Thus, we aim to review the proposed
NEP-dependent pharmacological mechanisms by which roflumilast can block
COVID-19-associated inflammatory, coagulopathy and fibrotic cascades.