It has been demonstrated that the latest outbreak-causing novel
coronavirus pneumonia (COVID-19) virus (2019-nCoV, SARS-CoV-2) invades
human alveolar epithelial cells primarily by angiotensin-converting
enzyme 2 ACE2 (Zhou et al., 2020). The SARS-CoV engages ACE2 for
cellular entry to produce final infection (Hoffmann et al., 2020).
Furthermore, Zhao et al documented that in human lungs, ACE2 is found
primarily in alveolar epithelial cells of type II (AT2), indicating that
this virus activates ACE2-positive AT2 cells to cause pneumonia (Zhao et
al., 2020). Recently an epidemiological research indicated that certain
patients with SARS-CoV-2 exhibit symptoms of severe liver injury (Chen
et al., 2020). The investigators also established that ACE2 is
significantly enriched in cholangiocytes by studying stable liver cells
at single-cell resolution (Chai et al., 2020), depicting that the virus
may bind ACE2-positive cholangiocytes directly causes dis-regulation
result in liver function. Now the main question arises that why ACE2 is
crucial for COVID-19 control and treatment strategies? Normally, ACE2
catalyzing the transformation of angiotensin-II into angiotensin-1–7.
Angiotensin-II acts on angiotensin receptor-1(AT1) and controls the
processes of vasoconstriction, apoptosis, proinflammatory changes, and
fibrosis cycle, while angiotensin 1–7 acts on Mas receptors induces
contrary symptoms (Paz Ocaranza et al., 2020 ). Thus any loss in the
activity of ACE2 in the alveolar cells may increase the level of
angiotensin II and result in acute respiratory distress. The expression
of ACE2 is comparatively higher in lung and a study documented the
protective role of ACE2 in lung injury (Imai et al., 2005). It was
proved in a mice model that acidic gas inhaled by mice downregulated
ACE2 and increased the level of Ang II in the lung and plasma of
wild-type mice, and the levels of Ang II in the lung. Further, the
research team found that recombinant human ACE2 (rhACE2) protein action
may reduce the plasma Ang II levels and reduce the risk of acute lung
injury in ACE2 Knockout mice. The binding mode of COVID-19 virus with
ACE2 and the clinical importance of renin-angiotensin System, revealed
that this system is extensively involved in the pathology of COVID-19
(Gurwitz, 2020; Vaduganathan et al., 2020). Mostly the COVID-19 patients
develop fever, inflammatory changes, and respiratory distress. It can be
hypothesized that these changes might be due to lack of ACE2 and
imbalance in renin-angiotensin system in the pulmonary interstitium.
Furthermore, Gurwitz suggested that telmisartan as an alternative choice
for treating COVID19 before the respiratory distress develops.
Interestingly, Zhang et al. noticed a low fatality rate in COVID-19
hypertensive patients that were exposed to Angiotensin converting enzyme
inhibitors (ACEIs) and Angiotensin receptor blockers (ARBs) than control
ones (Zhang et al., 2020). Hoffmann and his co-workers proved that
protease inhibitor-mediated blocking of Ace2 and Tmprss2 might be a
target in the prevention and treatment of COVID-19 (Hoffmann et al.,
2020).
Based on the above findings, we can speculate that the treatment
strategies for COVID-19 may include recombinant ACE2 therapy, hormones
such as estradiol, which increases the level of ACE2, and drugs that
decrease the level of angiotensin II.
Keywords: ACE2, Angiotensin II, Zoonosis, COVID19, therapeutic purpose