3.6 ET-1-reduced cAMP in COVID-19
Surprisingly, ET-1 is also
suggested to exaggerate the inflammation via inhibiting adenylate
cyclase (AC) activity and thereby, cAMP accumulation (Insel et al.,
2012).Within the immune system, cAMP is synthesized from ATP by the
action of AC to regulate the
anti-inflammatory effects (Gentile
et al., 1988). As reported, cAMP could decrease the production of
pro-inflammatory mediators as well as enhance the production of
anti-inflammatory factors in various immune cells (Raker et al., 2016).
Meanwhile, cAMP was concluded to promote ATP production that is
described to potentially improve the efficiency of innate and adaptive
immune systems for fighting off COVID-19 (De Rasmo et al., 2016;
Taghizadeh-Hesary and Akbari, 2020).
Consistent with these findings, it was reported that COVID-19 may be
more fatal in the elderly-population than in children, as with
increasing the age, there is a gradual decline in the
cellular ATP and subsequent
ATP-induced cAMP accumulation (Srivastava, 2017). Furthermore, tobacco
smokers, who suffer from a decreased content of ATP in immune cells, are
also found to be more susceptible for COVID-19 infection (MaliĆska et
al., 2019).
Regardless of age, males are generally more prone to die by COVID-19
than females (Jin et al., 2020). The finding which can be attributed to
sex hormone differences, since estrogen was recorded to potentially
induce ATP production during the inflammation than androgens (Kassi and
Moutsatsou, 2010). Additionally, the same strategy could be particularly
relevant for patients with seriously medical conditions, who showed an
immune dysregulation as a result of ATP-depletion (Zhou et al., 2020).
With increasing the number of SARS-CoV-2- infected cases globally, there
is unfortunately no time chance for discovering a newly therapeutic
agent. Taken together, directing most efforts towards vaccine production
may be of no avail at least nowadays, since millions of people
everywhere have been already infected with COVID-19, and they are in
urgent need for rapid treatment in order to prevent the disease
progression. In addition, developing anti-viral drugs needs a long way
to go. Therefore, the best choice may be repurposing the currently
available drugs which may greatly save time and money as well as secure
many people from death.