SARS-CoV-2 from Pathophysiology to Vaccine Development. In this PPT, I have tried to give a brief overview of the ongoing pandemic.

1. SARS-CoV-2 from Pathophysiology to
Vaccine Development
By
Arindam Sain
(CSIR- JRF, Department of Biotechnology, MAKAUT, W.B.)
PHYSIOLOGY NEWS

2. CORONA Virus
 Order- Nidovirales
Family- Coronaviridae
Genus- b-coronavirus
 Pathogenetic and Zoonotic in nature
 A spherical particle with crown like projection
 Average diameter- 125nM
 Viral envelope consists of lipid bilayer with anchored
proteins
 Nucleocapsid- N protein with positive sense single
stranded RNA genome
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3. 4 major structural proteins-
• Spike (S) protein
• Nucleocapsid (N) protein
• Membrane (M) protein
• The envelope (E) protein
Wrapp et al. , 2020
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4. THE LIFE CYCLE OF SARS-CoV-2 IN HOST CELLS
1. S protein binds to the cellular receptor ACE2
2. Conformation change in the S protein facilitates viral envelope
fusion with the cell membrane
3. SARS-CoV-2 releases RNA into the host cell
4. Genome RNA is translated into viral replicase polyproteins pp1a and
1ab
5. Cleavage into small products by viral proteinases
6. The polymerase produces a series of sub-genomic mRNAs by
discontinuous transcription
7. Translation into relevant viral proteins
8. Viral proteins and genome RNA are subsequently assembled into
virions in the ER and Golgi
9. Transportion via vesicles and released out of the cell
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5. Shereen et al., 2020PHYSIOLOGY NEWS

6.  After incubation period, virus causes non-
severe symptoms and elicits protective immune
responses
 Successful elimination of the infection relies on
the individual’s health status and the HLA
haplotype
 If the general health status and the HLA
haplotype of the infected individual do not
eliminate the virus, the patient then enters the
severe stage, when strong damaging
inflammatory response occurs, especially in the
lungs.
 At this stage, inhibition of hyaluronan synthase
and elimination of hyaluronan can be
prescribed.
 Cytokine activated mesenchymal stem cells
can be used to block inflammation and promote
tissue reparation.Yufang Shi et al., 2020
PROGRESSION OF COVID-19 INFECTION AND POTENTIAL ADJUVANT
INTERVENTIONS

7. HOST-PATHOGEN INTERACTIONS BETWEEN SARS-CoV2
AND THE HOST IMMUNE SYSTEM
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8. IMBALANCED HOST RESPONSE TO SARS-CoV-2
DRIVES DEVELOPMENT OF COVID-19
 SARS-CoV-2 infection induces
low IFN-I and -III levels with a
moderate ISG response
 Strong chemokine expression is
consistent
across in vitro, ex vivo,
and in vivo models
 Low innate antiviral defenses
and high pro-inflammatory cues
contribute to COVID-19
Daniel Blanco-Melo et al., 2020
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9. SCHEMATIC REPRESENTATION OF SARS-CoV-2-driven SIGNALLING
PATHWAYS AND POTENTIAL DRUG TARGETS.
Michele Catanzaro et al., 2020
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10. PHYSIOLOGY NEWS

11. HYPOTHETICAL MECHANISM BY SARS-CoV-2 IN ESTABLISHING AN
INFLAMMATORY FEEDBACK LOOP BETWEEN IL-6 AND
ANGIOTENSIN II
Michele Catanzaro et al., 2020PHYSIOLOGY NEWS

12. POSSIBLE PATHWAYS CONTRIBUTING TO HYPERACTIVATION OF
MONOCYTE-DERIVED MACROPHAGES AND HYPERINFLAMMATION
IN COVID-19
Miriam Merad and Jerome C. Martin, 2020PHYSIOLOGY NEWS

13. Possible contribution of hyperactivated monocytes to
coagulation in COVID-19
Miriam Merad and Jerome C. Martin, 2020
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14. Innate Immune Dysregulation in the Pathophysiology
of COVID-19
Cell 181, May 28, 2020
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15. Trained immunity is defined as an
enhanced innate immune response to
different pathogens after an initial
challenge, such as vaccination or infection.
Certain microbial ligands capable of
binding specific pattern recognition
receptors are able to induce durable
metabolic and epigenetic changes in innate
immune cells. This reprogramming of the
metabolic and epigenetic landscape of the
cell allows quick accessibility of
transcription factors to the promoter and
enhancer regions of pro-inflammatory
genes upon restimulation, facilitating gene
expression. The increased metabolic
activity of the cell affords fast supply of the
energy and metabolites necessary to mount
a robust immune response upon
restimulation. Combination of these
epigenetic and metabolic effects affords
increased responsiveness upon secondary
stimulation with the same or a different
ligand and can even protect against a
subsequent infection.
Trained Immunity Mechanisms and Improvement of Anti-
viral Host Defense
Cell 181, May 28, 2020 PHYSIOLOGY NEWS

16. Trained Immunity Can Be Used to Prevent the
Spread of New Infections
Cell 181, May 28, 2020PHYSIOLOGY NEWS

17.  Meta-analysis of human, non-
human primate, and mouse
single-cellRNA-seq datasets for
putativeSARS-CoV-2 targets
 Type II pneumocytes, nasal
secretory cells, and absorptive
enterocytes are ACE2+TMPRSS2+
 Interferon and influenza increase
ACE2 in human nasal epithelia
and lung tissue
 Mouse Ace2 is not upregulated by
interferon, raising implications for
disease modelling
Ziegler et al., 2020, Cell 181, 1016–1035
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18. DEVELOPING VACCINES AND THERAPEUTIC
ANTIBODIES FOR COVID-19
Sempowski et al., 2020
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19. PHYSIOLOGY NEWS

20. PHYSIOLOGY NEWS

21. PHYSIOLOGY NEWS

22. N Engl J Med 2020PHYSIOLOGY NEWS

23. A few alternative approaches……….

24. Potential therapeutic effects of
MSCs in respiratory lung injury
are mediated by different
mechanisms including but not
limited to secreted paracrine
factors, extracellular vesicles
(EVs), and possibly mitochondrial
transfer, promoting tissue
protection, immunomodulation,
and possibly viral resistance.
Khoury et al., 2020
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25. TARGETS AND POSSIBLE TREATMENTS FOR
COVID-19
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26. STEM CELLS IN COVID-19 - FROM A TARGET FOR VIRAL
INFECTION TO THERAPY WITH MESENCHYMAL STEM
CELLS (MSC)
Stem Cell Rev and Rep (2020) 16:434–440PHYSIOLOGY NEWS

27. POSSIBLE IMPACT OF HEPARIN IN
COVID-19
J Thromb Haemost. 2020;18:1020–1022.
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28. ANGIOTENSIN-CONVERTING ENZYME (ACE)
INHIBITORS AND ANGIOTENSIN RECEPTOR 1 (AT1R)
INHIBITORS
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29. PATHOGENESIS OF COVID-19 AND POTENTIAL
ADJUVANT USE OF MELATONIN.
R. Zhang, et al., 2020PHYSIOLOGY NEWS

30. NATURAL PRODUCTS MAY INTERFERE WITH SARS-COV-2
ATTACHMENT TO THE HOST CELL
A. A. ELFIKY., 2020
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31. THANK YOU
To be continued..
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