■ Healthcare
Continued From Page 28
naviruses such as SARS-CoV, MERS-CoV, and
SARS-CoV 2 is still poorly understood. What is
known is that when this event is triggered, the
body’s own innate immune responses in the
shotgun approach to eradicate the virus trigger
acute lung injury, which can, in some cases, be
fatal. In a patient dealing with chronic diseas-
es, this event may be too much to overcome and
may at least partially explain why individuals
with certain pre-existing conditions have higher
mortality ratios.
Q. Removing for a moment age and underlying
health conditions, why is the virus affecting differ-
ent people so differently?
A. There’s a variety of factors likely at play,
many of which are still in the process of coming
to light through scientific enquiry and testing. I
think it is worth mentioning that most cases of
COVID-19 are very mild. I am also mindful that
mild means many things to different people.
In mild cases it can range from signs and symp-
toms akin to a severe flu, to signs and symptoms
similar to that of the common cold. Many pa-
tients also report mild pneumonia, which is still
significant, but does not require hospitalization.
In addition, people may become infected and
never even know they have it. Many people in-
fected with SARS-CoV 2 are completely asymp-
tomatic and would never know they had it in the
absence of a test. Fortunately, children seem to
be the latter, though there have been some excep-
tions usually involving pre-existing conditions.
On that note, it is known that age is a factor,
which can be reproduced using mice in the lab.
The older the patient gets, the more likely the
risk of severe complications, with patients over
60 experiencing the most significant complica-
tions with the disease.
Q. There seems to have been some success in treating
the coronavirus with some drugs, including the ma-
laria drugs chloroquine and favipiravir. Can you tell
us more about that and why these drugs may work in
halting the disease in individuals?
A. Favipiravir inhibits the RNA-dependent
RNA polymerase of several notable RNA viruses
including the influenza virus. The RNA-depen-
dent RNA polymerase is an enzyme encoded in
the viral genome and produced by the cell
during infection.
The function of the RNA-de-
pendent RNA polymerase is to
replicate the viral RNA genetic
material that is used to make
progeny viruses. Without the
RNA-dependent RNA poly-
merase, the virus cannot
successfully replicate in the
cell and produce more vi-
ruses. For that reason, this
enzyme makes a very at-
tractive target for the devel-
opment of antiviral drugs
because it is vital for the
virus during replication and
is an enzyme that is not pres-
ent in a health host cell.
Therefore, drugs that direct-
ly attack this enzyme will kill the
virus with minimal effects on host
cells. Both the influenza virus and
SARS-CoV 2 are RNA viruses and thus use
30 COMMERCE www. commercemagnj.com
a similar RNA-dependent RNA polymerase to
accomplish the task of replicating the viral ge-
netic material. That said, the influenza virus
and SARS-CoV 2 are very different RNA viruses,
and it is very important to note this fact.
Aside from favipiravir, there’s a drug called
remdesivir that also targets coronavirus
RNA-dependent RNA polymerases. Remdesivir
is also being evaluated as an anti-SARS-CoV
2 therapeutic agent. It’s currently under tri-
als, and both antivirals are still far too early in
testing to definitively say they will reverse the
increasing number of SARS-CoV 2 cases in the
world. It’s also important to remember that due
to the nature of the SARS-CoV 2 RNA-depen-
dent RNA polymerase making mistakes during
replication, it is inevitable that drug resistant
populations of viruses will emerge. The pres-
ence of the antiviral may “select” for drug resis-
tant populations that eventually will no longer
respond to treatment. Therefore, continuing re-
search to identify novel SARS-CoV 2 inhibitors
will remain a top priority for some time.
For chloroquine, it has been reported that
this drug blocks the original SARS-CoV, as well
as several other human coronaviruses from in-
fecting cells. Essentially, it acts as a doorman
and denies the virus entry to the area of the cell
that the virus needs to complete its replication
cycle. There have been some encouraging re-
ports about chloroquine’s use as a therapeutic
to treat SARS-CoV 2 infections, but again, it’s
too early to definitely say that its use will be
effective in controlling the current pandemic.
There have also been reports of chloroquine
toxicity in patients, so it is very clear that even
if effective, chloroquine will not be a “one drug
treats all” for every case of COVID-19.