Could DIZE be the answer to COVID-19?

From Angiotensin II to Cyclic Peptides and Angiotensin Receptor Blockers (ARBs): Perspectives of ARBs in COVID-19 Therapy

“…The RAS system plays a pivotal role in cardiovascular homeostasis and the regulation of blood pressure. In addition, it was found that ACE2 receptors are an important element of the RAS system, as it converts ANG II to heptapeptides alamandine and aspamandine, which are beneficial for vasodilation and homeostasis [ 14 , 15 , 16 ] ( Figure 2 ). Figure 4 shows the main components of the renin–angiotensin system that are the counterbalancing axes: vasoconstriction axis (ACE/Ang II/AT1R), vasorelaxation axis (ACE2/A(1–7)/AT2R/MasR), and vasorelaxation axis (ACE2/alamandine/MRgD).…”

“…Essential π*-π* interactions between Tyr and Phe rings observed in ANG II and its superagonist Sar1 ANG II are missing in sarilesin. Furthermore, deletion of the aromatic amino acid phenylalanine at position 8 results in the vasodilator heptapeptides, aspamandine [ANG1–7] and upon decarboxylation alamandine ANG [Ala1-7], which counterbalance the toxic ANG II in the RAS system [ 14 , 15 , 16 ]. Figure 5 shows amino acid sequences for angiotensin II, sarilesin and sarmesin.…”

“…The ACE2 enzyme has been identified to be the binding site of SARS-CoV-2 virus and controversy rose if the RAS system could be a therapeutic target, as an option to treat the disease by blocking the binding [ 14 ]. Recent findings have shown that ARBs have protective effects in hypertensive patients infected by SARS-CoV-2 [ 53 , 54 , 55 , 56 , 57 , 58 , 59 ].…”

“…In particular, the strategy is to enhance the ACE2 enzyme which converts toxic ANG II to the protective antagonist heptapeptides ANG(1–7) and alamandine, maintaining homeostasis and at the same time blocking the entry of SARS-CoV-2 to ACE2 [ 14 ]. This is possible with ACE2 activators like DIZE [ 14 ] and with non-peptide mimetics of Ang II which upregulate ACE2, producing the two heptapeptides that counterbalance destructive ANG II and are beneficial for vasodilation. It is very likely that uncontrollable release of pathogenic ANG II may be one of the reasons for the storm of cytokines and pneumonia in COVID-19.…”

“…This function is generally acknowledged as a pivotal link between ACE2 deficiency and SARS-CoV-2 infection [ 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 ]. On the contrary, overexpression of ACE2 is linked with protection from SARS-CoV-2 [ 14 , 16 , 63 ]. Accumulated data presented in the cited articles show that RAS inhibitors improve clinical outcomes of COVID-19 patients with hypertension [ 66 ].…”