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1. CP - Core Microbiology > (3) Antivirals > Flashcards

(3) Antivirals Flashcards

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1
Q

How many people were living with HIV in 2012?

A

35.3 million

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2
Q

How many people were newly infected with HIV in 2012?

A

2.3 million

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3
Q

How many AIDS deaths were there in 2012?

A

1.6 million

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4
Q

Where is HIV most predominant?

A

Sub-Saharan Africa

Increasing epidemic in South and South-East Asia

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5
Q

What happens as HIV RNA copies rises?

A

CD4+ T cells decreases, immune system starts failing

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6
Q

What is an issue of antivirals?

A

Can get viral resistance if drug not taken consistently

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7
Q

What 2 classifications of infection do viruses cause and which is most common?

A
  • acute
  • chronic

Most viruses cause acute infections - body eradicates virus

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8
Q

Some viruses have RNA and some have DNA. In general, which causes acute and which causes chronic infection?

A

RNA = acute

DNA = chronic

but there are exceptions!

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9
Q

Give examples of acute viral infections

A
  • influenza
  • measles
  • mumps
  • hepatitis A
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10
Q

What are 2 further classifications of chronic viral infections?

A
  • latent with (or without) recurrences

- persistent

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11
Q

Give examples of latent chronic viral infections

A
  • herpes simplex

- cytomegalovirus

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12
Q

Give examples of persistent chronic viral infections

A
  • HIV
  • hepatitis B
  • hepatitis C
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13
Q

What does herpes simplex cause?

A

Cold sores

Latent in 75% of people, activates in 10%

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14
Q

What type of genetic material does Hep C virus contain?

A

RNA (an exception to the rule!)

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15
Q

What is special about the genetic material of HIV?

A

RNA converted to DNA by reverse transcriptase

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16
Q

What do viruses consist of?

A
  • nucleic acid (DNA or RNA)
  • protein (coat - structural, enzymes - non-structural)
  • +/- lipid envelope
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17
Q

Viruses are obligate intracellular parasites. What does this mean?

A

They can only replicate within cells, cannot reproduce outside their host cell

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18
Q

What 3 protein types does the HIV-1 genome code for?

A
  • core structural proteins
  • viral enzymes
  • envelope structural proteins (extra-cellular and intra-cellular)
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19
Q

Give 3 viral enzymes coded for in the virus genome

A
  • protease
  • reverse transcriptase
  • integrase
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20
Q

What are the stages in virus replication

A
  1. virus attachment to cell (via receptor)
  2. cell entry
  3. virus uncoating
  4. early proteins produced viral enzymes
  5. replication
  6. late transcription/translation - viral structural proteins
  7. virus assembly
  8. virus release
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21
Q

What is the purpose of virus uncoating?

A

Makes the genome available

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22
Q

What is a common target for molecular inhibition (anti-viral activity)?

A

Unique proteins encoded for by viruses, many of which are vital for virus replication and infectivity

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23
Q

Which enzyme do most antivirals target?

A

Polymerases

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24
Q

Which cells’ polymerases convert DNA to DNA

A
  • eukaryotes

- DNA viruses

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25
Q

Which cells’ polymerases convert DNA to RNA

A
  • eukaryotes

- DNA viruses

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26
Q

Which cells’ polymerases convert RNA to RNA?

A
  • RNA viruses
27
Q

Which cells’ polymerases convert RNA to DNA

A
  • retroviruses (HIV)

- hepatitis B virus

28
Q

What is a nucleotide made up of?

A
  • base
  • triphosphate
  • ribose sugar
29
Q

What was AZT (azidothymidine) originally developed as?

A

Developed in 1965 as an anti-cancer drug

30
Q

What happened to AZT in 1985?

A

It was found to inhibit HIV replication

31
Q

What type of drug is AZT (azidothymidine)?

A

Nucleoside Reverse Transcriptase Inhibitor (NRTI)

32
Q

What do NRTIs?

A

They inhibit reverse transcriptase!

33
Q

What are 2 types of NRTIs?

A
  • pyramidine analogues (thymidine analogues and cytosine analogues)
  • purine analogues (adenine and guanidine)
34
Q

Give a specific thymidine analogue (NRTI)

A

Zidovudine

35
Q

Give a specific cytosine analogue (NRTI)

A

Lamivudine

36
Q

Give 2 purine analogues (NRTIs)

A

Abacavir

Tenofovir

37
Q

As well as HIV, which other virus also contains reverse transcriptase enzyme?

A

Hepatitis B virus (HBV)

38
Q

Which NRTIs are also active against HBV as well as HIV?

A
  • lamividine

- tenofovir

39
Q

What are NNRTIs?

A

Non-nucelotide reverse transcriptase inhibitors

40
Q

Give 2 NNRTIs

A
  • efavirenz

- nevirapine

41
Q

Give examples of protease inhibitors (PIs)

A
  • atazanavir
  • darunavir
  • fospamprenavir
  • lopinavir
  • nelfinavir
  • ritonavir
  • saquinavir
42
Q

Ritonavir is used as a “boost”. What does this mean?

A

It is used to boost the levels of other PIs allowing reduced dose of these other drugs and therefore reduced side effects

43
Q

Give 3 types of newer HIV drugs

A
  • fusion inhibitor
  • integrase inhibitor
  • chemokine receptor antagonist (co-receptor)
44
Q

Give a fusion inhibitor (new HIV drug)

A

Enfuviritide (T20, given by IM injection)

45
Q

Give an integrase inhibitor (new HIV drug)

A

Raltegravir

46
Q

Give a chemokine receptor antagonist (co-receptor) (new HIV drug)

A

Maraviroc (CCR-5)

47
Q

What are the 7 specific stages in HIV infection?

A
  1. fusion of HIV to the host cell surface
  2. HIV RNA, reverse transcriptase, integrase, and other viral proteins enter the host cell
  3. viral DNA is formed by reverse transcriptase
  4. viral DNA is transported across the nucleus and integrates into the host DNA
  5. new viral DNA is used as genomic RNA and to make viral proteins
  6. new viral RNA and proteins move to the cell surface and a new, immature HIV forms
  7. the virus matures by protease releasing individual HIV proteins
48
Q

What are the co-receptors on the host cell that HIV uses?

A

CCR5 or CXCR4

49
Q

What is HAART?

A

Highly active antiretroviral therapy

  • 2NRTIs + NNRTI
  • 2NRTIs + boosted PI
50
Q

When is HAART started?

A

When CD4 falls

51
Q

What is the aim of HAART?

A

To switch off virus replication

52
Q

How long is HAART taken for?

A

Life long

53
Q

Why are there now problems with HAART?

A

Now problems with toxicity

54
Q

How many nucleotides does the HIV genome contain?

A

Around 9,000 nucleotides

Every genome will contain at least one mutation

55
Q

The HIV genome can contain mutations which give resistance to certain antivirals. Which mutation results in resistance to Lamivudine?

A

M184V

In presence of Lamivudine, the rare population of strains with this mutation will soon predominate

56
Q

There is some evidence for the cure of HIV infection by what?

A

CCR5 delta 32 stem cell transplantation

57
Q

What achieved cure rates of 40-90% for hepatitis C?

A

Interferons and ribavirin

58
Q

We now have interferon free regimens with what percentage cure rate for all strains of Hepatitis C?

A

> 90%

59
Q

For acute infections, antivirals only tend to work if given when?

A

Soon after symptoms develop

60
Q

Give an important antiviral for Herpes Simplex Virus (HSV) and Varicella Zoster Virus (VZV)

A

Aciclovir

a nucleoside analogue - phophorylated by herpes virus thymidine kinase

61
Q

Give an important antiviral for cytomegalovirus (CMV)

A

Ganciclovir

62
Q

Give an important antiviral for Influenza

A

Oseltamivir and Zanamavir

neuraminidase inhibitors

63
Q

Give an important antiviral for Hep C and RSV

A

Ribavirin

64
Q

Give an important antiviral for Hep C and Hep B

A

Interferons

1. CP - Core Microbiology (8 decks)

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