Therapeutic approach Pros Cons Comments
ACE Inhibitors (ACEIs) Mitigates effects of ANG II in relevant cell types/tissues involved in COVID-19 pathobiology Well-established clinical utility Well defined PK and PD Large amount of preclinical animal data Oral administration. Possible inhalable administration Generic Drugs, with established production, supply chain and handling Does not salvage the protective effects of ACE2 inhibited by SARS-CoV-2 Dry cough is common side effect May not be effective in tissues with high Chymase expression (e.g., heart) Challenges with drug interactions, hypotensive patients, other side effects
Potential for rapid (compassionate) use in at-risk patients and for rapid (repurposing) clinical trials.
Angiotensin Receptor Blockers (ARBs)
Mitigates effects of ANG II (via AGTR1) in relevant cell types/tissues involved in COVID-19 pathobiology Long track record of clinical use Well defined PK and PD Large amount of preclinical animal data Oral administration. Possible inhalable administration Generic Drugs, with established production, supply chain and handling Does not salvage the protective effects of ACE2 inhibited by SARS-CoV-2 Challenges with drug interactions, hypotensive patients, other side effects Will not impede possible pathological effects of AGTR2
Potential for rapid (compassionate) use in at-risk patients and for rapid (repurposing) clinical trials.
Recombinant soluble ACE2
‘Rescues’ ACE2 activity inhibited by SARS-CoV-2 infection via action as a ‘decoy’ for the virus Mitigates effects of ANG II in relevant cell types/tissues involved in COVID-19 pathobiology Substantial preclinical data in animals Limited data from human studies; unknowns regarding safety Limited information regarding dosing, target engagement, PK, PD etc. Higher costs + more complicated handling, new supply chain Infusion is required
Additional preclinical studies needed, in parallel with early-phase trials
ANG (1-7)
Engages protective MAS1 signaling, mitigating harmful effects of ACE2 inhibition by SARS-CoV-2 Very limited data from human studies Less available preclinical data than for the other options Limited information regarding dosing, target engagement, PK, PD etc., all Indirectly inhibits pathological ANG II signaling Higher costs + more complicated handling, new supply chain Infusion is required
Additional preclinical studies needed. Unclear that human trials are justified.