Week 21: (C) Emerging viral Diseases Flashcards
What is the R rate?
the average number of people 1 person will infect
What is the growth rate?
quickly the numbers of infections are changing day by day. If the growth rate is greater than 0 (+ positive), then the epidemic is growing. If the growth rate is less than 0 (- negative) then the epidemic is shrinking.
What is the difference between R rate and growth rate?
R alone does not tell us how quickly an epidemic is changing.
Different diseases with the same R can generate epidemics that grow at very different speeds.
For instance, 2 diseases, both with R=2, could have very different lengths of time for 1 infected individual to infect 2 other people; one disease might take years, while the other might take days.
What are the 2 strategies for dealing with Covid?
mitigation
suppression
What is mitigation strategy?
focuses on slowing but not necessarily stopping epidemic spread reducing peak healthcare
demand while protecting those most at risk of severe disease from infection,
reduce peak health care demand
What is suppression?
which aims to reverse epidemic growth, reducing case numbers to low levels and
maintaining that situation indefinitely.
What are examples of mitigation?
optimal mitigation policies (combining home isolation
of suspect cases, home quarantine of those living in the same household as suspect cases, and social
distancing of the elderly and others at most risk of severe disease)
How might mitigation reduce peak healthcare demand and deaths?
2/3 and deaths by half
What is the preferred strategy option?
suppression
What is the major challenge with suppression?
this type of intensive intervention package, or something
equivalently effective at reducing transmission will need to be maintained until a vaccine becomes
available (potentially 18 months or more), given that we predict that transmission will quickly rebound
if interventions are relaxed
What are features of Covid DNA?
Contain a positive sense, single stranded RNA
genome of 27-32 kb
What is S, E, M and N?
The 3’ terminal 1/3 of the genome encodes
structural proteins including envelope
glycoprotein spike (S), envelope (E),
membrane (M) and nucleocapsid (N)
What are features of the 5’ end terminal?
The 5’ terminal 2/3 of the genome encodes a polyprotein, pp1ab which is further cleaved into
16 non-structural proteins involved in genome
replication and transcription
What type of RNA does COVID have?
positive sense
What is directly translated in COVID?
ORF1a produces pp1a
What cleaves up the pp1a protein?
viral protein
3CLpro
its a protease
What does 3CLpro do?
cute the viral protein up into its constituent parts
What does ORF1a and ORF1b produce?
pp1ab
How are proteins 12, 13, 14, 15 and 16 on pp1ab produced?
by ribosomal frame shifting
What gene is predominantly made in covid?
ORF1a
but ORF1b can be produced by ribosomal frame shifting
how are the ORF 1b constituents cleave?
viral protease
What is the virus trying to do?
block the host immune response
What happens to the cleaved proteins?
the replicase polyproteins go onto replicate the viral genome
What are pp1a and pp1b?
replicase polyproteins
What type of strand does the replicase protein produce?
a negative strand of RNA
makes a subgeneric mRNAs
What does the subgeneric mRNAs code for? (ER)
N, E, S proteins
Where do the proteins go through?
Golgi complex
How does the virus obtain the proteins?
picks them up on the surface of the GC as the virus buds through
What is the receptor for covid?
Angiotensin-converting enzyme 2
ACE2
What is the target for anti-hypertensive drugs?
ACE2
What are the 2 functions of the S protein?
recognise host R
brings about membrane fusion
How many lobes does the spike protein have?
3 lobes that can move up and down
How does the S protein bind to the ACE2?
when a lobe flips up it can bid to an ace2, eventually binding to one on each lobe so 3 all together
What happens to the structure of the 3 bound S protein?
opens up, exposes the core of the protein which is involved in membrane fusion
What part of the S protein punches its way into the host cell membrane?
CORE
and delivers the virus into the cell
What is exposed when the S protein undergoes the confo change?
membrane fusion region
How is the membrane fusion region activated?
proteinic cleavage
cellular enzyme called furins recognise the highly exposed loop in the side the virus.
If they clip the loop it releases these alpha helixes (CORE)
which become exposed when it opens up. this cleavage causes the spike protein to open up.
What happens in mild disease?
monocytes produce the production of interferon, induces production of antiviral molecules (innate response)
the antibodies they make can recognise and neutralise the spike protein.
What happens in people with severe disease?
the fc domains the antibodies bind to CD32B on the cell surface of the virus
This surpasses the interferon response
Individuals with severe COVID-19 have anti-spike antibodies in which the Fc domain,
binds to CD32B. This interaction sends a signal to block expression of interferon-regulated genes.
When does the antibody bind to CD32B?
The CD32B receptor dampens such immune responses
if it is bound by another protein. b
What are covid test?
> PCR
“Lateral flow” tests
Reverse transcription loop-mediated isothermal amplification (RT-LAMP)
What enzyme converts RNA to DNA?
reverse transcriptase
What is the difference between RT-LAMP and PCR?
Reverse transcription loop-mediated isothermal
amplification (RT-LAMP)
—> no specialist equipment needed, just cont temp (60 degreesC)
PCR
—> primers replicate a strand and so on, exponential
detected by a dye
need a PCR machine
How is amplification detected in RT-LAMP test?
pH
Magnesium ions
Why do we detect pH and Magnesium ions on RT-LAMP?
The amplification reaction causes pH to lower and Mg2+ levels to drop
What indicators show cages in pH and Magnesium ions?
Phenol red, for pH, and hydroxynaphthol blue (HNB)
Magnesium. Another option is to use SYBR Green I, a DNA intercalating colouring agent.
What is the function of the Oxford Uni-AstraZeneca vaccine? (cheapest one)
viral vector (genetically modified virus)
stabilised version of spike protein on vector
DOES NOT cause the virus itself
Induces antibody response and T cell mediated immune response.
NEED both
memory T cells + antibodies
What are the Moderna and Pfizer-BioNTech vaccines?
RNA capped sequence to code for the spike protein enclosed in lipid nano particles and injected not the muscle.
need to be kept at low temps
