Advancing scientific Knowledge in times of Pandemics

1. ADVANCING SCIENTIFIC KNOWLEDGE IN TIMES OF
PANDEMICS
DEVELOPING THERAPEUTIC STRATEGIES AND CURRENT
KNOWLEDGE ON DRUGS FOR TREATMENT OF COVID-19
PRESENTED BY
V.LAVANYA
II YEAR,
B.PHARM.
C.L.BAID METHA COLLEGE
OF PHARMACY,
CHENNAI.

2. ABSTRACT:
 Despite intense research there is currently no effective vaccine available against the new severe acute
respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged in the later 2019 and responsible for the
COVID-19 pandemic. This infectious and communicable disease has become one of the major public health
challenges in the world. The clinical management of COVID-19 has been limited to infection prevention and
control measures associated with supportive care such as supplemental oxygen and mechanical ventilation.
 Meanwhile efforts to find an effective treatment to inhibit virus replication, mitigate the symptoms,
increase survival and decrease mortality rate are ongoing. Several classes of drugs, many of them already in
use for other diseases, are being evaluated based on the body of clinical knowledge obtained from infected
patients regarding to the natural history and evolution of the infection. Herein I will provide an updated
overview of the Developing therapeutic strategies and current knowledge on drugs and therapeutic agents
being tested for the prevention and treatment of COVID-19. These include different classes of drugs such as
antiviral agents (chloroquine, ivermectin, nitazoxanide, hydroxychloroquine, lopinavir, remdesivir,
tocilizumab), supporting agents (Vitamin C, Vitamin D, azithromycin, corticosteroids) and promising
investigational vaccines. Considering the controversies and excessive number of compounds being tested and
reported in the literature we hope that this review can provide useful and updated consolidated information on
potential drugs used to prevent, control and treat COVID-19 patients worldwide.

3. INTRODUCTION:
• Epidemics and pandemics have been threatening the human race
time and again. SARS, H1N1, Ebola, and more have shown their
teeth in the past, but with each such outbreak, we are learning new
ways of fighting and managing such unexpected diseases that can
potentially kill millions of people. Technology cannot prevent the
onset of the pandemics; however, it can help prevent the spread,
educate, warn, and empower those on the ground to be aware of the
situation, and noticeably lessen the impact. Today, with converging
technologies , it has become possible to test several innovative
approaches to pandemic response.

4. DEVELOPING THERAPEUTIC STRATEGIES:
• The need of the hour is to develop drugs against this deadly virus –
which is easier said than done. Before we come up with strategies to
fight the virus, we need to study its behaviour closely to understand
which of its essential processes we can target.
• THREE MAIN APPROCHES:
 Targeting SARS-CoV-2 binding to
the host cell
 Targeting SARS-CoV-2 replication inside
the host cell
 Repurposing already approved drugs

5. STRATEGY 1:Targeting SARS-CoV-2 binding to the host cell
• A group of researchers led by Jason McLellan from the University of Texas
published a detailed structure of the viral ​“S” protein and highlighted how it is
used by the virus to bind to the host cell. This study demonstrated that the virus
uses a ​“Lock and Key” mechanism to attach itself to the host cell, which is the
first step in the infection process. Key – ‘S’ Protein & Lock – ACE2
• A group of researchers from the Leibniz Institute for Primate Research,
Germany, working under the leadership of Stefan Polhmann demonstrated that
another protein, TMPRSS2 assists in viral entry into the host cell by priming the
spike protein ​“S.
STRATEGY 2:Targeting SARS-CoV-2 replication inside the host cell
• A study by a group led by Rolf Hilgenfeld at the University of Lubeck, Germany,
described the detailed structure of another viral protein, Mpro, which plays an integral
role in viral replication. The researchers showed that the reproduction of the virus
inside the cells could be blocked by using an inhibitor, α-ketoamide, thereby offering a
promising strategy for potential therapeutic intervention.

6. STRATEGY 3 : Repurposing already approved drugs
• Alternate strategies for treating COVID-19 may stem out of
repurposing drugs that are already in the market for other diseases
and disorders.
• Eg . Remdesivir , an antiviral drug
Combination of Azithromycin and Hydroxychloroquine.
Current therapeutic treatment for COVID-19 related to the onset and
physiopathology of the disease
DRUG STRUCTURE ACTION
Azithromycin Antiviral , anti-
inflammatory.
Favipiravir Antiviral, RNA-dependent
RNA polymerase inhibitor

7. Remdesivir
Inhibits RdRp polymerase
inhibiting RNA synthesis
Chloroquine
Increases endosomal pH and
alters glycosylation of ACE-2,
interfering with virus/receptor
interaction.
Hydroxychloroquine
Increases endosomal pH and alters
glycosylation of ACE-2, interfering
with virus/receptor interaction.
Umifenovir (Arbidol)
Interacts with spike glycoprotein and
impedes its trimerization, which is key
for host cell adhesion and hijacking
Vitamin C & D
Immunomodulatory property. Boosts
immunity by stimulating IFN
production , enhancing neutrophil
phagocytic capability.

8. RESULTS & DISCUSSION :
The present outbreak caused by SARS-Co-2 was indeed expected. Similar to previous
outbreaks, the current outbreak will also be contained shortly. However the real question is, how
are we planning to counter the next zoonotic CoV epidemic that is likely to occur with in the
next 5-10 years or perhaps within lesser time?
 Do the increasing technological advancement of the human race and changing ecology have
anything to do with this? Epidemiological data and genetic sequence analysis show that many of
these coronavirus strains might date as far back as ~ 5000BCE or even earlier. Many of these
originated in animal hosts, particularly bats. These viruses have undergone mutations and
exchanged hosts several times before transferring to humans. Are the changing climate,
increasing pollution, and modernization in any way responsible for inducing critical mutations
in these viruses, that enable them to be transferred to humans? Why are bats resistant to such
viruses?
These questions prompt different perspectives, and hence alternate approaches to solve these
mysteries. The answers to these questions might be critical in dealing more effectively with this
kind of crisis. If anything, this global pandemic has paved the way to the inevitable realization
that the development of a supportive environment towards promoting scientific culture and
temperament is essential towards tackling such pandemics in the future.

9. CONCLUSION:
• Despite great efforts worldwide to try to find an effective drug against SARS-
CoV-2 yet there is not a consensus about a definite therapy for COVID-19.
The use of repurposed medications has shown to be a good alternative with
promising results while an effective vaccine is still not available.
• Despite the great challenge posed by the COVID-19 pandemic and the
surfaced ethical issues, the ongoing efforts to fight the virus and the
excellence and hardworking of many research groups across the world offer
hope that in a near future we can win this battle.
• The most powerful message that has come out of all this is that the human
race is capable of presenting a united front against a crisis, in spite of
whatever geographical, racial, and religious borders may exist. With a species
so determined to persist, a minuscule virus won’t be able to defeat us so
easily.

10. REFERENCE:
• World Health Organization. https://www.who.int/dg/speeches/detail/who-
director-general-s-opening-remarks-at-the-mission-briefing-on-covid-19--
• Y. Chen, Q. Liu, D. Guo
Coronaviruses: genome structure, replication, and pathogenesis
• J. Med. Virol., 92 (4) (2020), pp. 418-423, 10.1002/jmv.25681
• B. Damle, M. Vourvahis, E. Wang, J. Leaney, B. Corrigan
• Clinical Pharmacology Perspectives on the Antiviral Activity of Azithromycin
and Use in COVID‐19
• Clin. Pharm. Therap. (2020), 10.1002/cpt.1857
• Remdesivir and chloroquine effectively inhibit the recently emerged novel
coronavirus (2019-nCoV) in vitro.
• Structures from National Center for Biotechnology Information. PubChem
Database. https://pubchem.ncbi.nlm.nih.gov