The COVID19 virus has plagued the world, as a cellular and molecular
biologist, I am presenting this commentary after careful analysis of the
genomic structure of the virus and its effects on the lungs.
Why does it affect the older generation more compared to young adults
and children?
The free radical theory of aging proposes that organisms age because
they accumulate oxidative damage1-3. I postulate this
causes the older population to have an increase in reactive oxygen
species (ROS) 4-7, which partially reduces metabolites
of molecular oxygen generated as by-products of various cellular
processes, such as respiration1,8. This creates a
condition of hypoxia, particularly in the lungs as the lung volume and
capacity decreases with age9.Another interesting
phenomena to note is that severe acute respiratory syndrome (SARS-CoV)
virus, which is genetically similar to corona virus, are known to
proliferate in hypoxia conditions. Hence, making the older generation
more susceptible to disease.
Another point to be noted is the lungs are highly vulnerable to viral
infection as the express increased cell surface proteins that the
viruses use to gain entry into the cell10. Latest
research shows that ACE2 (Angiotensin-converting enzyme 2) has been
identified as a potential SARS-CoV2 receptor and is highly expressed in
the lungs11-12. One of the severe manifestations of
corona virus is lung fibrosis, even when the patient is recovered, the
lung function declines by 20-30%13-15. The initiation
of lung fibrosis occurs as ROS species are generated by NADPH oxidase-4
(NOX4), the pathway it triggers is angiotensin II (AngII) type 1
receptor (AT1R) axis which causes increased ROS production in lung
fibroblasts16. Angiotensin-converting enzyme 2 (ACE2)
counteracts this inhibition via the RhoA/Rock pathway by reducing
NOX4-derived ROS16. My hypothesis is that as the
SARS-CoV2 virus enters the bloodstream, infecting the lung cells, it
uses all the available ACE2 receptors, which causes an elevation in
AngII-AT1R axis, which leads to activation of NOX4-derived ROS-mediated
RhoA/Rock pathway, creating a hypoxic environment, this further
facilitates viral multiplication and causes chronic obstructive in the
lungs. Therefore, pharmacological antioxidants can act as potential drug
targets in this scenario.
In layman’s terms- for this virus to multiply, it requires hypoxic
conditions and it creates this by attacking the lung surface protein
that prevents hypoxia. Potentially, if we have more antioxidants in our
body the lesser chance of the virus finding the ideal conditions to
proliferate.