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Immunology and infection > Antiviral Therapies > Flashcards

Antiviral Therapies Flashcards

1
Q

Microcephaly

A

Zika virus

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2
Q

Definition of a virus

A

Obligate intracellular parasites

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3
Q

What is the composition of a virus

A

Genome comprised of DNA nad RNA

Viral genome is replicated and directs th synthesis

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4
Q

Examples of symmertrical protein capsid

A

Adenovirus

Picornavirus

Calicivirus

Non-enveloped

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5
Q

Examples of eneveloped virus

A

Lipid envelope derived from host membrane

Pleimorphic: measles virus (variation in size)

Ebola virus

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6
Q

Examples of combination of capsid and envelope

A

Herpes virus

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7
Q

How is a virus named

A

The disease: polio

Person who discovered it: epstein barr

Place it was discovered: coxsackievirus

Part of the body affected: rhinovirus, hepatitis

Way it is spread: dengue, influenza

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8
Q

What is the negative sense

A

Complimentary strand of the messenger RNA

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9
Q

What are the consequences of viral genome type

A

RNA viruses and retroviruses use own polymerase to replicated - lack proof reading capacity high mutation rate

RNA less stable - size is limited

RNA viruses use complex codign stragies to make more proteins

DNA are big - accessory genes are not essential but can modify the host immune response, often lost in passage in culture

Segmented genomes - allows additional easy form of recombination, but imposes more difficult packaging stategies

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10
Q

How many influenza virus are made for every 1 entering the cell

A

1000 are made

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11
Q

What is the cytopathic effect

A

Death of the cell caused by virus

Lysing of the cell

Shut down of host protein synthesis or accumulation of viral proteins

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12
Q

Viruses form plaques

A

As the virus has replicated, it kills cells and leaves a hole which is stained clear

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13
Q

How is plaque assay useful

A

Can see how many viruses present

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14
Q

What si syncytia assay

A

Viruses with surface portein that fuse cells together

HIV

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15
Q

Viral diagnosis

A

Genome: PCR, RT-PCR

Antigen: IFA, ELISA - use antibodies to stain cells

Virus particles: electron microscopy

Cytopathic effect - virus isolaiton

Antibodies against virus - serology

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16
Q

How do we manipulate viruses

A

So small they can be synthesised

Introduce synthetic DNA or RNA - driven to replicate

Allows reverse genetics - engineer vaccinations

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17
Q

Why is it hard to treat viruses

A

Infect host cells - cannot target those

Have to find things that viruses do that host cell doesn’t

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18
Q

What do most of the antiviral drugs do

A

Target viral enzymes - by rational drug design

Nucleoside analogues - inhibit with nucleic acid replication - however need to element of specificity

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19
Q

What is acyclovir

A

Nucleoside analogue

Looks like guanosine

Whole bottom half is missing so 3’ - OH cannot attach in nuecleotide chain, prevention of phosphodiester bond

Chain terminator

20
Q

Why is acyclovir so good for specificity

A

Exist in its unphophorylated form

Aciclovir can only be phosphorylated by viral thymidine kinase only encoded in herpes virus

Rest of the steps are using cellular enzymes

aciclovir tirphosphate has higher affinity for viral DNA polymerase than host cell

21
Q

What is remdesivir

A

nucleoside analogue

analogue of adenose - chain termination 3 nucleotides downstream

it twists the shape of the molecule so no more nucleotides can be added

used for ebola but more recently used for COVID

22
Q

What is important for an antiviral drug

A

Target a unique and essential gene

Be effective against a range of influenza types

Be easy to administer even to very sick patients

Few side effects

23
Q

How does adamantanes/rimantadine work

A

Cyclic amines with bulky cagelike structures

Byproducts of petroleum refinement

Active against influenza A molecule

TARGET: Sit in the middle of a tetrameric ion channel specifically coded by influenza virus known as M2 ion channel

M2 allows H+ from acidic enviornment of endosome to virus core

Undo interactions holdign virus together

Release of genome by uncoating of virus

24
Q

Resistance to adamantadine

A

Single point mutation on M2 for amantadine to no longer bind (S31N)

Little cost to fitness

Most H3N2 are resistant

H5N1 bird flu

Swine flue pH1N1

25
Q

What type of structure is neuraminidase

A

Tetrimeric

26
Q

Why is neuraminidase important in the replication cycle

A

Virion budds out

If no NA hemagglutinin will stick back down to the sialic acid

Neuraminidase enzyme that cleaves sialic acid

Enable virus to be released

27
Q

How long do NAI shorten illness

A

17 hrs to 29hrs

28
Q

Retrospective analysis of tamiflu use in 2009 pandemic

A

Halved risk of death if started within 48 hours of symptoms

29
Q

What are examples of neuraminidase inhibitors

A

Relenza

Tamiflu

30
Q

What are the resistance to osetamivir

A

Histatine to tyrosine 274

H1N1 - 2007/08

31
Q

Are all 4 NAI circulating today susceptable to NAI

A

yes

32
Q

What is baloxavir

A

Viral polymerase of influenza structure has been solved

Baloxavir inhibits PA endonulcease enzyme

33
Q

Baloxavir resistants

A

Single point mutation PA I38T

Mutation observed in H3N2 after treatment in children

34
Q

Facts about hepatitis C virus

A

Foudn its way in blood products

170 million people are are infects

4% will have carcinoma

35
Q

Why aren’t people with HIV cured

A

HIV retrovirus

Integrates itself into the DNA

Reservior cells

36
Q

Who are the people who are cured of HIV

A

Blood marrow transplant

Using people who are resistant to HIV - mutation in CCR5 gene at delta 52

Makes CCR5 not expressed

HIV cannot enter new cells

37
Q

What are biological virus treatment

A

Passive immunotherapy - anitbodies from recovered individuals

38
Q

What is plaivizumab

A

Humanized monoclonal anitbody against F fusion protein

Against RSV

55% reduced hospitalisation

39
Q

What viral drugs don’t work for COVDI

A

Ribavirin

Chloroquine

Lopinavir

Ritonavir

40
Q

What other treatments are there for COVID

A

M protease inhibitors

Remdesivir

Favipiravir

Toculizimab - IL6 antibody

Dexamethasone - steroid

41
Q

What is the difference in patients who are given remdesivir

A

The more oxygen and mechanical ventilation - the more ineffective the treatment

42
Q

What is the difference in dexamethasone for treatment of SARS

A

Dexamethasone more effective in mechanical ventilation

43
Q

What is the future for antiviral therapy

A

New antiviral therapies that target the host

Broad acting antivirals

Combinations of drugs

Delivery systems suitable for target population

D

44
Q

Why is relenza not as good as a drug as tamiflu

A

Chemistry of relenza means that virus more readily acquires resistance

45
Q
A

Immunology and infection (14 decks)

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