Trials to treat Covid.

19 pandemic by drug repurposing or novel agents

Introduction:

Coronavirus disease (COVID-19) is an infectious disease caused by a newly

discovered coronavirus that causes respiratory illness in hosts. In most cases,
COVID-19 causes mild symptoms including dry cough, tiredness, and fever.
started at the end of 2019.
With the paucity of new drugs to combat this disease, the medical
community is in a race to identify repurposed drugs that may be effective
against this novel coronavirus. Some of these drugs are:
Remdesivir (VEKLURY®)

is a broad-spectrum antiviral medication. is an intravenous nucleotide

prodrug of an adenosine analog. Remdesivir is the first treatment for
COVID-19 to be approved by the US Food and Drug Administration (FDA).
was initially developed for the treatment of Ebola virus

Mechanism of action:

Remdesivir is an adenosine nucleotide prodrug that distributes into cells

where it is metabolized to a nucleoside monophosphate. The nucleoside
monophosphate is subsequently phosphorylated by cellular kinases to form
the pharmacologically active nucleoside triphosphate metabolite (GS-
441524).

Remdesivir triphosphate (RDVTP) acts as an analog of adenosine

triphosphate (ATP). This active form remdesivir (available in the cytoplasm)
is utilized by the cell viral RNA dependent RNA polymerase instead of the
adenosine during the process of viral genetic material replication which is
incorporated into the growing viral genetic strand instead of adenosine.
`
This incorporation in the viral genetic material not only delayed chain
termination during the replication process but also unable to repair viral
genetic materials.
Chemical structure:

Favipiravir (Avigan)
Favipiravir (T-705) is a synthetic prodrug, is a purine base analogue, is an
antiviral medication used to treat influenza in Japan. available in both oral
and intravenous formulations.

Mechanism of action:
Favipiravir (prodrug) is a purine base analog that is converted to active
favipiravir ribofuranosyl-5B-triphosphate (favipiravir-RTP) by intracellular
phosphoribosylation.
It is a selective and potent inhibitor of RNA-dependent RNA polymerase
(RdRp) of RNA viruses.
There are several hypotheses as to how favipiravir-RTP interacts with RNA
dependent RNA polymerase.
a. This molecule acts as a substrate for the RNA-dependent RNA-
polymerase (RdRp) enzyme, which is mistaken by the enzyme as a purine
nucleotide, thus inhibiting its activity leading to termination of viral protein
synthesis.
b. It gets incorporated in the viral RNA strand, preventing further extension.

Chemical structure:
Oseltamivir (Tamiflu)
is an antiviral medication used to treat and prevent influenza A and influenza
B (flu), Oseltamivir is in a class of medications called neuraminidase
inhibitors. It works by stopping the spread of the flu virus in the body.

Mechanism of action:
Oseltamivir is an ethyl ester prodrug requiring ester hydrolysis for
conversion to the active form, oseltamivir carboxylate which is a potent and
selective inhibitor of virus neuraminidase enzymes(Viral neuraminidase
enzyme activity is important for viral entry into uninfected cells, for the
release of recently formed virus particles from infected cells, and for the
further spread of the infectious virus in the body.), which are glycoproteins
found on the virion surface.

Chemical structure:

Conclusion :

In my point of view, I think that this pandemic will end soon because the
health professionals are putting so much effort as well as the people. They
are now taking this pandemic so seriously ,they are so aware These days
and welling to get rid of this virus as soon as possible, Furthermore
awareness is needed so the number of cases will come down and it will be
easy to find a cure .We cannot stop something that is meant to be but we can
try and by continuous trial, we can survive from it.
 References

1- Agrawal, U., Raju, R., & Udwadia, Z. F. (2020). Favipiravir: A new and emerging antiviral option in
COVID-19. Medical journal, Armed Forces India, 76(4), 370– 376.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7467067/#:~:text=Favipiravir%2
0(T%2D705)%20is,found%20to%20have%20antiviral%20activities.

2- National Center for Biotechnology Information (2020). PubChem Compound Summary for CID 492405,
Favipiravir. Retrieved November 10, 2020 from https://pubchem.ncbi.nlm.nih.gov/compound/Favipiravir.

3- National Center for Biotechnology Information (2020). PubChem Compound Summary for CID 65028,
Oseltamivir. Retrieved November 10, 2020 from https://pubchem.ncbi.nlm.nih.gov/compound/Oseltamivir.

4- Richard T. Eastman, Jacob S. Roth, Kyle R. Brimacombe, Anton Simeonov, Min Shen, Samarjit Patnaik,
and Matthew D. Hall.(2020). Remdesivir: A Review of Its Discovery and Development Leading to
Emergency Use Authorization for Treatment of COVID-19.
ACS Central Science ,6(5), 672 -683. https://doi.org/10.1021/acscentsci.0c00489