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 (MaliƄska 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.