Exogenous Administration of ACE2
The administration of a large amount of soluble form of ACE2 could represent an intriguing opportunity, since excessive ACE2 may exert dual functions: (a) competitively bind SARS-CoV-2 to neutralize the virus and/or slow viral entry in the host cell; (b) rescue cellular ACE2 activity, which negatively regulates RAAS and may theoretically exert a protective effect in lung injury (Verdecchia et al., 2020a). A pilot clinical study is currently investigating the efficiency of a recombinant human angiotensin-converting enzyme 2 (rhACE2) in patients with COVID-19 (Zhang H. et al., 2020).
Recombinant human ACE 2, rhACE2 (hrsACE2, APN01, GSK2586881), sequesters circulating viral particles interfering with S-protein binding to its host target, beside its role in regulating the systemic RAAS. Taken together, these activities may offer therapeutic benefits in COVID-19 patients, although the large molecular weight of the protein may potentially limit its effects on local RAAS (Gheblawi et al., 2020). rhACE2 has already undergone phase 1 and 2 clinical trials in healthy volunteers and in a small cohort of patients with ARDS (Khan et al., 2017). Moreover, it has been demonstrated that rhACE2 can significantly block the early stages of SARS-CoV-2 infections in engineered human blood vessel organoids and human kidney organoids (Monteil et al., 2020). In this context, Procko (2020) was able to engineer hACE2 sequences to obtain soluble receptors able to sequester SARS-CoV-2 RBD and inhibit its cell attachment. Remarkably, combinatorial mutants enhanced ACE2 binding to SARS-CoV-2 RBD by an order of magnitude, as compared to the wild type receptor form, and targeted ACE2 mutations might provide further improvement.
Additionally, the availability of ACE2 nanoparticles applied to nose filters, chewing gums, clothes, filters and gloves could be of help in sequestering the virus thus preventing its entry into the host (Aydemir and Ulusu, 2020). Prevention virus transmission could represent a more convenient strategy than therapeutic interventions on viral infection, avoiding interference with ACE2 and disturbance of the finely regulated RAAS axis (Aydemir and Ulusu, 2020).