Angiotensin receptor blockers as tentative SARS‐CoV‐2 therapeutics

Abstract

At the time of writing this commentary (February 2020), the coronavirus COVID-19 epidemic has already resulted in more fatalities compared with the SARS and MERS coronavirus epidemics combined. Therapeutics that may assist to contain its rapid spread and reduce its high mortality rates are urgently needed. Developing vaccines against the SARS-CoV-2 virus may take many months. Moreover, vaccines based on viral-encoded peptides may not be effective against future coronavirus epidemics, as virus mutations could make them futile. Indeed, new Influenza virus strains emerge every year, requiring new immunizations. A tentative suggestion based on existing therapeutics, which would likely be resistant to new coronavirus mutations, is to use available angiotensin receptor 1 (AT1R) blockers, such as losartan, as therapeutics for reducing the aggressiveness and mortality from SARS-CoV-2 virus infections. This idea is based on observations that the angiotensin-converting enzyme 2 (ACE2) very likely serves as the binding site for SARS-CoV-2, the strain implicated in the current COVID-19 epidemic, similarly to strain SARS-CoV implicated in the 2002-2003 SARS epidemic. This commentary elaborates on the idea of considering AT1Rblockers as tentative treatment for SARS-CoV-2 infections, and proposes a research direction based on datamining of clinical patient records for assessing its feasibility.

Cardiovascular Considerations for Patients, Health Care Workers, and Health Systems During the COVID-19 Pandemic

“…As the ACE2 receptor is the mechanism of entry for SARS-CoV2, some data suggest that ACE inhibitors (ACEi) and angiotensin receptor blockers (ARB) may upregulate ACE2, thereby increasing susceptibility to the virus (Figure 1) (5). In contrast other studies show that ACEi/ARB may potentiate the lung protective function of ACE2, which is an angiotensin II inhibitor (80)(81)(82). Thus, the therapeutic implications for ACEi/ARB therapy during COVID-19 infection is unclear.…”

Comorbidities in COVID-19: Outcomes in hypertensive cohort and controversies with renin angiotensin system blockers

“…Thus, the upregulation of ACE-2 receptors by the use of RASB over time in older people may emulate ACE expression in young people. It is also possible that having more ACE-2 receptors and increased ACE-2 functions will likely produce more angiotensin (1e7) that might provide resilience against target-mediated destruction and development of pulmonary failure in patients with COVID-19 [22]. This postulated positive effects on lung can be also protective during overwhelming infection with COVID-19.…”

COVID-19 Coronavirus spike protein analysis for synthetic vaccines, a peptidomimetic antagonist, and therapeutic drugs, and analysis of a proposed achilles’ heel conserved region to minimize probability of escape mutations and drug resistance

“…But more worryingly still, the situation is not settled, and physicians and patients could take action in the wrong direction. Gurwitz [81] has emphasized that the picture is even more complex. He examined reports from China suggesting that a mechanism of production of lung injury during the viral infection may be due to excess free angiotensin-II, which might be displaced from ACE2 by the SARS virus particles.…”