Antivirals Flashcards

1
Q

Structure of virus

A

Genetic materia (RNA or DNA)

Surrounded by capsid (protein shell surrounding the genetic material of the virus)

SOME HAVE:
Then lipid envelope + envelope proteins

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2
Q

Tropism of hepatits

A

Liver hepatocytes

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3
Q

T/f there is a cure for hep B and hep c

A

F….. there is no cure for hep B… it is chronic infection

there is now a cure for hep C (=ribavarin))

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4
Q

What type of genetic information in hep B

A

DNA

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5
Q

Which drug used to treat hep B

A

Initial treatment is pegylated interferon alpha 2a

then

Tenofovir/lamivudine = nucleotide analogue,

(also a reverse transcriptase inhibitors )

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6
Q

What type of virus is hep C

A

RNA

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7
Q

What was hep C treated with

A

Interferon

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8
Q

Wht is the current hep C treatment

A

Ribavirin & Peginterferon alfa

Ribavirin = nucleoside analogue prevents viral RNA synthesis

Boceprevir = protease inhibitor
-Most effective against Hep C genotype 1

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9
Q

HIV: Attachment and entry phase

A
  • Viral membrane proteins interact with leukocyte membrane receptors
  • Viral capsid endocytosis
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10
Q

HIV: Replication and integration

A

Within cytoplasm - reverse transciptase enzyme converts viral RNA to DNA

DNA transported into nucleus & integrated into host DNA via integrase

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11
Q

HIV: assembly and release

A

Host cell’s ‘machinery’ utilised to produce viral RNA & essential proteins

Virus is assembled within cell –> mature virion is released

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12
Q

Receptors involved in attachment and entry of HIV

A

HIV Glycoprotein (GP)120 attaches to CD4 receptor

GP120 also binds to either CCR5 or CXCR4

GP41 penetrates host cell membrane & viral capsid enters

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13
Q

Drugs affecting HIV entry into host cell

A

Enfuvirtide
-Binds to HIV GP41 transmembrane glycoprotein

Maraviroc
-Blocks CCR5 chemokine receptor

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14
Q

What drugs affect HIV replication

A

Nucleoside RT inhibitors
Activated by 3 step phosphorylation process
E.g. Zidovudine

Nucleotide RT inhibitors
Fewer phosphorylation steps required
(also used for Hep B)
E.g. Tenofovir

Non-nucleoside RT inhibitors
No phosphorylation required
Not incorporated into viral DNA
E.g. Efavirenz

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15
Q

Outline drugs interfering with HIV integration

A

Integrase inhibitors

Raltegravir - first of 3 licensed integrase inhibitors

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16
Q

What is the use of HIV protease i assembly and release

A

Gag precursor –> encodes all viral structural proteins

HIV protease cleaves Gag precursor protein

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17
Q

Which drugs are protease inhibitors

A

Saquinavir - 1st generation PI

Low dose Ritonavir reduces PI metabolism –> co-administered as ‘booster’

Boceprivir is a PI used to treat hep C

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18
Q

What type of genetic material does HSV have

and what is the structure

A

Double-stranded DNA

Surrounded by tegument & enclosed in a lipid bilayer

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19
Q

State the different types of HSV

A

Herpes Simplex Virus (HSV)-1 –> cold-sores

HSV-2 –> genital herpes

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20
Q

Which drug is used for HSV?

A

Nucleoside analogues –> Aciclovir

A guanine analogue

Used in CMV and EBV too

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21
Q

What type of genetc material on influenza

A

Multipartite single stranded RNA virus

22
Q

What are the two envelope proteins on HIV

A

Neuroaminidase/haemagglutinin

23
Q

What is neuramindase important for

A

Release of the virus

24
Q

Tropism of influenza

A

Multipartite single stranded RNA virus

25
Q

What is the treatment for influenza

A

Neuraminidase inhibitor –> Oseltamivir or zanamivir

Virus cannot be released from the cell

26
Q

T/F olsetamivir is very efficacious

A

F… doesn’t reduce rate of hospitilisation

(probably because there is a few days of incubation in which influenza is replicating in cells but you’re aymptomatic at this point. By the time you realise you have flu then take it, too many cells have already been infected. Better to take flu vaccine)

27
Q

Why are viruses unable to reproduce on their own

A

Since they do not have a defined cellular structure or their own metabolism

So referred to as obligate parasites

28
Q

What does the viral genetic material contain information for

A

contains:
1. The information that is required to create its own microenvironment
2. Program the synthetic machinery of th`e host cell for viral replication.

29
Q

What is the function of the viral capsid

A
  1. protect the genetic material from dangers such as nucleases in the external environment.
  2. an also play an important role in attachment of the virion to the host membrane, which would ordinarily repel the negatively charged DNA or RNA.
30
Q

What is the nucleocapsid

A

he capsid and the viral genome along with any associated nucleoproteins are referred to as the nucleocapsid.

31
Q

Where is the lipid envelope (derived from

A

A number of viruses also have a protein coat, which is a lipid bilayer quite often derived from the membrane of the host cell

Integral membrane proteins and glycoproteins coded for by the viral genome.

These integral membrane proteins often play an important role in the entry and exit of viruses into host cells.

32
Q

6 stages of typical life cycle of virus

A
  1. Viral attachment
  2. Entry
  3. Uncoating
  4. Replication
  5. Assembly
  6. Release
33
Q

Outline the three methods of viral entry into cells

A

Clathrin-mediated endocytosis.

Caveolar endocytosis

Plasma membrane fusion

34
Q

Why is uncoating important and what is carried out by

A

This refers to removal of the PROTEIN CAPSID.

This occurs so that the genetic material can come into direct contact with the cellular machinery that it will utilise for replication

degradation of the capsid involves a variety of different proteins and enzymes, which are produced by both the host cell and the virus.

35
Q

Outline the type of replication that occurs for each of the following types of virus:

  1. +ve ssRNA
  2. -ve ssRNA
  3. Dipliod +ve ssRNA retrovirus
  4. Double stratnded RNA
  5. DNA virus
A
  1. +ve ssRNA: These can produce proteins (i.e. induce translation) directly by utilising the hosts’ ribosomes
  2. -ve ssRNA: hese cannot produce protein directly and must contain the appropriate transcriptase allowing the host ribosome to create the complementary +ve RNA strand.
  3. Dipliod +ve ssRNA retrovirus: These contain a reverse transcriptase enzyme allowing the host cell to produce DNA from the viral genome
  4. Double stranded RNA: contain all the necessary templates to produce the proteins and RNA templates required for replication.
  5. DNA virus: These viruses generally have the means for transportation into the host nucleus.
36
Q

Differentiate +ve and -ve ssRNA in terms of replication

A

+ve ssRNA can induce translation directly (i.e. can act as mRNA molecule)

-ve ssRNA cannot produce protein directly (must contain a transcriptase to convert it into +ve ssRNA for reading by ribosome

37
Q

Outline how assembly can differ between viruses

A

Differs depending on whether the virus has lipid envelope

NON-EVELOPED: Just requires construction of capsid

ENVELOPED: closely associated with the release stage and involves the formation of ‘docking stations’ within the host membrane by viral proteins. Once the viral proteins have replaced the host proteins in the membrane the nucleocapsid attaches itself (i.e. docks) to the inner surface of the membrane

38
Q

Outline the release phase of virus lifecycle and the differently types

A
  1. Disintegration of host cell
  2. Budding (host cell in tact)

For enveloped viruses once the nucleocapsid is attached to the ‘docking station’ it becomes wrapped up within the patch of membrane and ‘buds’ off into the extracellular environment.

39
Q

Structure of HIV including genetic material

A

Large

2 copies of ssRNA in icosahedral capsid.

This in turn is surrounded by a phospholipid envelope containing numerous transmembrane glycoprotein complexes

40
Q

Which cells can HIV infect

A

HIV has the ability to infect a variety of immune cells including CD4+ T-lymphocytes, monocytes and macrophages.

41
Q

First ARV?

A

Zidovudine

42
Q

How are the following named hepatitis viruses spread

A

HAV/HEV fection result in very similar symptoms and can be controlled by good hygiene and sanitation

HBV spready by exposure to infected blood or bodily fluid

HCV spread through blood contact (mainly infected needles or blood transfusions)

43
Q

What is a subviral satellite

A

it requires another virus (in this case HBV) to assemble and infect new cells.

=HDV

44
Q

What is the consequence of chronic HBV infectin

A

Although around 95% of adults spontaneously recover from the illness, chronic infection
can lead to life threatening complications such as cirrhosis.

45
Q

What is the consequence of long term hep c infection

A

The majority of individuals who are acutely infected become chronically infected, which can lead to advanced liver disease and hepatocellular carcinoma.

(differs to HBV, where 95% spontaneously recover)

46
Q

What type of virus is varicella zoster and what can it cause in childhood and adultood

A

Herpes

Varicella zoster is responsible for causing chicken pox upon primary infection. Chicken pox is a highly contagious acute illness generally affecting young children, resulting in itchy lesions (pox)
on the skin.

Once the illness has resolved the virus is not eliminated and lies latently within the nerve cell bodies. The virus can subsequently become reactivated many years later causing shingles.

47
Q

What is treatment for varicella zoster

A

The antiviral compounds recommended for the treatment of HSV and varicella zoster include the nucleoside analogue aciclovir.

Same as other herpes

48
Q

How many segments of the influenza genetic material

A

multipartite genome of linear single-stranded RNA divided into 7-8 segments

49
Q

How is influenza transmitted

A

highly contagious and is transmitted through the air or via numerous bodily secretion

50
Q

Clinical manifestation of influenza

A

fever, cough, myalgia and general malaise.