8.2. Inhibition of Renin Activity: Aliskiren
An alternative approach is to inhibit the RAS pathway at its origin by inhibiting renin enzymatic activity. Regarding renin inhibitors, aliskiren is the sole compound in this class of drugs that was approved by the US Food and Drug Administration in March 2007 and commercialized for the management of hypertension [186]. Aliskiren may be used alone or in combination with other drugs to face COVID-19, in particular the severe forms of SARS-CoV-2 infection. Indeed, in patients with severe symptoms of COVID-19 hypoxia might have upregulated both arms of the RAS. Therefore, aliskiren might be a useful “tool” to reduce production of Ang I, the necessary fuel for both ACE and ACE2 hyperactivity and their detrimental effects. Aliskiren treatment in rats has been shown to upregulate both AT1R and MasR expression probably as consequence of a compensation mechanism when both Ang II and Ang (1–7) ligands are reduced by renin inhibition [187]. Of particular interest in the context of SARS-CoV-2 infection, the treatment has been shown to reduce expression of both AT2R and ACE2, thus possibly performing a multiple action in inhibiting both arms of the RAS [187]. Similarly, cation chelating agents such as CaNa2EDTA or nicotianamine might also work, although at different levels.