ACE2 receptor blockers: a novel therapeutic approach for COVID-19

Author(s): Kaustav Chakraborty, ERS Member (India)

While the novel coronavirus SARS-CoV-2 is spreading across the world, infecting more than one million people, the fact that no specific drug or vaccine exists against any of the coronaviruses including the SARS, MERS and the novel coronavirus is creating fear among the people. India’s COVID-19 count rises sharply day by day (active cases count 5,709 among, which 199 are dead according to as of 10 April, 2020). Hydroxychloroquine is the only ray of hope now-a-days, along with different vaccine trials and passive immunisation therapy using ‘convalescent plasma’, target-specific drug discovery is of paramount importance right now.

It has been well-known that SARS-CoV-2 appears to be optimized for binding to the human receptor ACE2 (angiotensin-converting enzyme 2) [1]. The spike (S) glycoprotein of 2019-nCoV binds ACE2 with higher affinity than SARS-CoV S [2]. Wrapp et al., (2020) also tested several published SARS-CoV RBD (receptor binding domain)-specific monoclonal antibodies and found that they do not have appreciable binding to 2019-nCoV S [2]. ACE2 is expressed in a variety of different tissues including both the upper and lower respiratory tract, myocardium and the gastrointestinal mucosa [3]. It has been demonstrated quite handsomely that increased ACE2 expression in airways of current (but not former) smokers and those with COPD [4]. So there is a chance-factor of the increased risk of viral respiratory tract infection in active smokers and virus-related exacerbations in those with COPD.

Angiotensin receptor blockers (ARBs) have effects that are similar to angiotensin converting enzyme (ACE) inhibitors, but ACE inhibitors act by preventing the formation of angiotensin II rather than by blocking the binding of angiotensin II to muscles on blood vessels. ARBs are used for controlling high blood pressure, treating heart failure, and preventing kidney failure in people with diabetes. Therefore, angiotensin receptor blockers (ARBs such as losartan, valsartan, telmisartan, etc) can be a novel therapeutic approach to block the binding and hence, attachment of SARS-CoV-2 RBD to ACE2-expressing cells, thus inhibiting their infection to host cells.

Covid-19 blog