PMC:7408073 / 101488-103319 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7408073","sourcedb":"PMC","sourceid":"7408073","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7408073","text":"Different routes of MLN-4760 treatment administration can be pursued depending on the hospital condition/expertise. In this exceptionally critical situation, it could be delivered to critical untreatable patients as a controlled “compassionate use”, in particular by inhalation. However, when, under hypoxic conditions, both arms of the RAS are upregulated, it might have a limited action and, by shifting the balance of ACE/ACE2 ratio in favour of ACE, might be even dangerous. Instead, specific inhibition of ACE2 enzymatic activity might effectively work in preventing the establishment of positive feedback loops in COVID-19 patients who are suffering from mild symptoms of the disease. MLN-4760 is sold by different companies, that, in case it works, could be encouraged to manufacture the molecule, actively contributing to face this global threat. On the other hand, the drug could be also synthesized in University chemistry labs because, to my knowledge, is no longer under patent restriction. MLN-4760, whose clinical development was abandoned after phase I trials (clinical name, ORE1001), is actually an interesting compound that could be useful for all patients in which a specific ACE2 upregulation is proven and associated to different (heart/lung/liver/intestine/kidney/immune system/blood/coagulation, etc.) pathological conditions related to ACE2 pathway downstream events, as it seems to occur in COVID-19 patients. Although in blood of normal subjects sACE2 activity is undetectable because its catalytic activity in human plasma is masked by an endogenous inhibitor [116] and chronic ACE2 activation may be deleterious, some patients might need of sACE2 activity to better face an acute pathological condition, therefore a careful monitoring of clinical parameters should be performed during patient 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