Biochemistry of Swine Flu

SMPatel
 Clinical Features
Great overlap among
Common cold
Seasonal Flu
Swine flu
Bird Flu

Laboratory tests are only way to

differenciate them
 ClinicalFeature Common Seasonal
Cold Flu
Fever <100'F >100'F
Headache, Bodyache + +++
Weakness + +++
Running nose, sneeze, +++ +
Sore throat
Spread Sinus, Bronchi,
Middle Ear Lung
 ClinicalFeature Swine Flu Seasonal
Flu
GIT Spread +++ +
Bronchi, Lung +++ +
Spread
Diarrhea, Vomiting +++ +
Pneumonia +++ +
Bronchitis
Enchephelitis +++ +
What is the reason for difference
in clinical features?
✔
Man are collection of molecules
✔
Swine flu viruses are collection of
molecules
✔
They react with each other

✔
The answer lies in understanding
molecular interaction between them
 Major causative organisms

Common cold Swine Flu Seasonal

Flu
Rhinovirus Influenza virus
Stucture of Influenza Virus

Electron Microscopy
 Stucture of Influenza Virus
H N
1 1
2 2
3 3
. .
. .
. 11
18
Capsid and
membrane
 Major causative organisms

Common cold Swine Flu Seasonal

Flu
Rhinovirus Swine Human
origin origin
Influenza Influenza
virus virus
S-OIV
H1N1 H3N2
 Hemagglutinin

Trimeric Sialic acid binding sites (3)

Sialic acid binding sites (3)

HA
Top View
 What the hell is sialic acid?
It is a monosaccharide
It is neuraminic acid derivative

It is present in glycoprotein
It is present in glycolipids

GP, GL are present on cell surface

Neuraminic acid
Anomers of Neu
Neuraminic Acid + Various Groups Diversity in the sialic acids

=Sialic Acids

Acetyl,
Methyl,
Neuraminic Sulphate,
Acid Phosphate,
Essentials of Glycobiology
Second Edition Chapter 14, Figure 2
Glycol-O(CH2)2OH
 What the hell is sialic acid?
It is a monosaccharide
It is neuraminic acid derivative

It is present in glycoprotein
It is present in glycolipids

GP, GL are present on cell surface

 Oligosaccharide chain with
Sialic acid

Such chains are bound to

membrane protein/lipid
forming Glycoprotein and Glycolipid
 Hemagglutinin

Trimeric Sialic acid binding sites (3)

Sialic acid binding sites (3)

HA
Top View
 Oligosaccharide chain with
Sialic acid

There is glycosidic bond between

Terminal sialic acid and adjesent
Galactose
Respiratory Upper respiratory
Stomatch
Intestine
Brain
H1, H5 H3
 ClinicalFeature Swine Flu Seasonal Flu
H1N1 H3N2
GIT Spread +++ +
Bronchi, Lung +++ +
Spread
Diarrhea, Vomiting +++ +
Pneumonia +++ +
Bronchitis
Enchephelitis +++ +
 Stucture of Influenza Virus
M2 Ion
channel
M2 ion channel functions.

acids change
structure of
capsids/envelop

Destroy capsid
Assembly

RNA enter
cytoplasm
M2 ionchannel in viral
Capsid and envelop

Rx M2blocker

Amantadine
Rimantadine

Resistance
 Neuraminidase
Cleavage of Resp.tract mucin

Hemagglutinin is sialo-glyco-protein
So Virus can bind each other via their
own H and Sialic acid
This aggregate virus when released
from cell

Hemagglutinin is un-sialated by
Neuraminidase, helping spread
 Neuraminic acid

Laninamivir
Oseltamivir
Zanamivir
Peramivir

Rx Neuraminidase inhibitors
Influenza A and B viruses carry two surface glycoproteins,
the haemagglutinin (HA) and the neuraminidase (NA). Both
proteins have been found to recognise the same host cell
molecule, sialic acid. HA binds to sialic acid-containing
receptors on target cells to initiate virus infection, whereas
NA cleaves sialic acids from cellular receptors and
extracellular inhibitors to facilitate progeny virus release and
to promote the spread of the infection to neighbouring cells.
Numerous studies performed recently have revealed that an
optimal interplay between these receptor-binding and
receptor-destroying activities of the surface glycoproteins is
required for efficient virus replication. An existing balance
between the antagonistic HA and NA functions of individual
viruses can be disturbed by various events, such as
reassortment, virus transmission to a new host, or
therapeutic inhibition of neuraminidase. The resulting
decrease in the viral replicative fitness is usually overcome
by restoration of the functional balance due to compensatory
mutations in HA, NA or both proteins
Get Swine Flu to servive
against humans