Viral pandemics Influenza and Coronaviruses Flashcards
What are three requirements for a virus to become a pandemic?
Novel antigenicity.
Replicate efficiently in human cells.
Transmit efficiently between people.
What is the natural reservoir of influenza A viruses?
A. Pigs
B. Chickens
C. Ducks
D. Tigers
C. Ducks
Which protein in human cells can support influenza replication?
ANP32 proteins are essential host cofactors- support influenza polymerase activity.
How can influenza polymerase utilise shorter mammalian ANP32?
Utilise ANP32 homologues by mutation in PB2 subunit.
Sngle amino acid change in PB2 E627K.
What needs to change in order for virus to successfully infiltrate humans?
Incoming virus needs to penetrate mucus + infect epithelial cells.
What contributes to incompatibility of avian-origin influenza virus with human respiratory tract?
Low acidic pH of URT followed by neutral pH of LRT
Why is influenza A currently incompatible with human-human transmission?
Avian influenza HA must adapt by acquiring affinity for human receptors.
Influenza entry is pH dependent + HA protein is pH sensitive.
Are antiviral medications for influenza used together or separately?
Antiviral medications for influenza are NOT licensed to be used together (like HAART).
What are examples of neuraminidase inhibitors?
Oseltamivir
Zanamivir
What do new influenza antivirals target?
Polymerase acidic protein endonucleases.
What is an example of a polymerase acidic protein endonuclease inhibitor?
Baloxavir
The influenza vaccine given to those at greater risk of complications from flu in the UK is:
A. A live attenuated virus.
B. A purified fraction containing HA and NA of an inactivated virus.
C. A purified HA protein expressed in insect cells.
D. An immunoglobulin fraction from sera of immune patients.
B. A purified fraction containing HA and NA of an inactivated virus
What are the two types of influenza vaccine given in the UK?
Inactivated vaccine
Live attenuated vaccine
What are features of the inactivated influenza vaccine?
Split or subunit- HA rich
Given to those at risk
Short term strain specific immunity mediated by antibody to HA head
What are features of the live attenuated influenza vaccine?
Cold adapted virus limited to URT
Given to children
Broader more cross reactive immunity including cellular response
What is the major influenza viral antigen?
Haemagglutinin
What is the structure of a influenza spike protein (HA)?
Where do most broadly neutralising Abs (bnAb) target?
HA stalk/ stem
To which parts of HA do current influenza vaccines generate a response?
Current vaccines generate specific Ab responses raised against immunodominant HA1 epitopes at 5 antigenic sites (Sa, Sb, Ca1, Ca2, Cb).
What are coronaviruses?
RNA genomes, single stranded +ve sense RNA, very large genomes.
Enveloped virions. 100nm
Nidovirales - A nested set of mRNAs from one large genome
Which coronaviruses have caused disease in humans?
OC43, 229E, NL-63 + HKU-1 cause 20-30% common colds
SARS + MERS are zoonotic
What do SARS and SARS-CoV2 bind to?
Angiotensin Converting Enzyme 2
What causes the severe effects of coronavirus?
Virus dissemination
Immunopathology
A COVID patient in ITU is most likely to benefit from:
A. Kaletra, a combination of lopinavir and ritonavir usually used to treat HIV.
B. Hydroxychloroquine, an antimalarial.
C. Remdesivir a nucleoside analogue.
D. Dexamethasone, a steroid.
D. Dexamethasone, a steroid.
Why is dexamethasone used in COVID patients on ventilation?
Cheap + extensively used steroid.
RECOVERY trial found Dex was effective in those receiving oxygen or ventilated.
Reduced deaths in ill-est cohort by 1/3.
Now standard of care in UK.
Which monoclonal antibodies have been trialed against COVID?
Regeneron
Sotrovimab
Which small molecule antivirals have been trialed against COVID?
Molnupiravir: Targets polymerase, nucleoside analogue.
Paxlovid: Targets protease.
Why is the COVID vaccine not effective against the Omicron variant?
Omicron has a large no. of Spike mutations that affect antibody neutralization.
