ACE Inhibitors
(ACEIs)
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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
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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
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Potential for rapid (compassionate) use in at-risk patients and for
rapid (repurposing) clinical trials.
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Angiotensin Receptor Blockers (ARBs)
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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
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Potential for rapid (compassionate) use in at-risk patients and for
rapid (repurposing) clinical trials.
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Recombinant soluble ACE2
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‘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
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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
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Additional preclinical studies needed, in parallel with early-phase
trials
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ANG (1-7)
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Engages protective MAS1 signaling, mitigating harmful effects of ACE2
inhibition by SARS-CoV-2
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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
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Additional preclinical studies needed. Unclear that human trials are
justified.
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