BIOSCI 106

Chemistry of Life

Associate Professor Christopher Squire

c.squire@auckland.ac.nz
An image from the video “Powering the Cell: Mitochondria.” Credit Robert A. Lue
 LECTURE 6
“Snotty pigs and
saving whales”
(molecular recognition and catalytic mechanism)

Associate Professor Christopher Squire, c.squire@auckland.ac.nz

Cover art from “The Pig and the whale” by Bill Dahlin and illustrated by Cedric Honhnstadt
Influenza
 Learning Objectives
Influenza as an exemplar of molecular recognition
• Explain how molecule recognition determines the
emergence and host range of viral diseases
• Describe the role of neuraminidase and hemagglutinin
surface proteins in the influenza life cycle
• Explain the role of domesticated animals in the spread
of influenza and why it is difficult for humans to be
infected by wild bird influenza strains
• Apply the concepts learned previously (e.g. weak
interactions, bond polarity, electronegativity) to explain
the sialic acid cleavage mechanism of influenza
neuraminidase or ANY simple enzymatic reaction you
are presented with
 Viral emergence in stages
1 2 3 4 5

Virus emerges Animal reservoir Intermediate host Human disease Dissemination

Longevity Transmission Transmission to humans

Low virulence Adaptation Mutation and adaptation to humans
Asymptomatic Virulence? Transmission between humans

Species “hopping” Species “hopping”

Intermediate Host Examples
WHEN HUMANS AND ANIMALS
INTERCEPT, DISEASE CAN CROSS
SPECIES BARRIERS

Plague Ebola MECHANISMS/CAUSES:

1347 2014

• Land use/encroachment
• Domestication
• Farming practices
MERS SARS
2012 2002
• Trade/Travel/tourism
• Consumption/ “bush meat”
• Climate
• Population changes
 Intermediate Hosts
SARS-CoV-2 and influenza A
SARS-CoV-2
Influenza
?
?
?
bat pangolin +

• INFECTED ~1 billion
• DEATHS 290,000 – 650,000
• FATALITY % Below 0.01
• ORIGINS & HOST RANGE:
o Wild bird source
o Animal domestication
OR maybe this toad? o Mutation
(Toady McBatface) o Recombination
Host cell recognition

Influenza A SARS-CoV-2

Virus • neuraminidase • spike

surface • hemagglutinin
protein
Host cell • sialic acid • ACE2
receptor receptors receptor
Influenza – entry and exit
Hemagglutinin
molecular recognition
of sialic acid

Neuraminidase
molecular recognition
of sialic acid + cleavage

DOI: 10.1183/09031936.00186214

SELF-LEARNING: https://www.youtube.com/watch?v=7Omi0IPkNpY
Sialic acid recognition/cleavage

sialic acid galactose

neuraminidase

Is the sialic acid linkage above from birds or humans?

BIRD? HUMAN?
 Public Health Message

MYTHBUSTERS – BLUE SNEEZE

Sneezing at 150 km/hr!
https://www.youtube.com/watch?v=qKiQA5e-fPg
 Public Health Message
• Elbow sneeze effective

• Make sure it’s your own elbow

Host range and virulence
 Why don’t wild bird flus
infect us?
• 16 types of HA:
H1….H16
9 types of NA:
N1….N9
• All found in birds
• Only three types have
adapted to infect
humans so far
H1 H1N1 (1918)
H2 H2N2 (1957)
H3 H3N2 (1968)
 Why don’t wild bird flus
infect us?
HUMAN
α-2,6 linkage

BIRD SARS-CoV-2

• All HAs extremely similar

• Bird HAs bind to receptors where sialic acids have
a2,3 linkages (bird cells)
α-2,3 linkage
• Human-adapted HA binds to sialic acid receptors with
a2,6 linkage (human cells)
Pigs and humans actually have both types – important
Why don’t wild bird flus
infect us?
α-2,6-SA receptors
α-2,3-SA receptors

α-2,3-SA receptors
40°C
39°C
swine
viruses

bird
viruses
human
viruses

33°C

α-2,6-SA receptors

α-2,3-SA receptors
37°C
PANDEMIC - Pigs as mixing
vessels
Public Health Warning

Never get too friendly with pigs

 Public Health Warning

Never get too friendly with pigs

or bats

or pangolins
Cleavage Mechanism – molecular recognition
by neuraminidase and catalysis
BINDING
Can you break this
mechanism down into
parts and understand the
catalysis using the
concepts of
intermolecular
interactions, polarity
and partial charge?
CLEAVAGE

Hope so. It will be

help you with your
post lecture quiz –
your trickiest one
yet!
 One mechanism clue
In the initial binding event, the sialic acid ring changes conformation from
chair to boat. The boat conformer is higher energy and this new conformation
promotes the catalysis through a high energy transition state (not shown).

Enzyme active sites

are meant to
stabilise transition
states
A final word on saving
the whales
 Do whales have snot?
• Yes, like us they catch
flu, get snotty and
sneeze
http://www.youtube.com/watch
?v=_YduOgdqXYk

• Snot sampling by
remote control
helicopter
(http://www.youtube.com/watch?v=-
iaFAPybD0M)
 Saving the whales!
• Findings – whales have picked up
human flu from whale watching
activities!

• Note to self:
–to save the whales don’t
sneeze down whale blow
holes
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