3 - Antivirals

Question 1

Clinical latency in HIV

Answer 1

CD4 T cell count dropping while HIV RNA slowly rising. When HIV RNA exceeds CD4 cells you get onset of symptoms

Question 2

Acute virus examples

Answer 2

Influenza, measles, mumps, hep A

Question 3

Chronic latent viral examples

Answer 3

Herpes simplex, cytomegalovirus

Question 4

Chronic persistent viral occurrences

Answer 4

HIV, Hep B, Hep C

Question 5

Virus structure

Answer 5

nucleic acid (DNA or RNA)
Protein coat
Sometimes lipid envelope

Question 6

Viral replication process

Answer 6

Virus attachment to cell (via receptor)
Cell entry
Virus uncoating
Early proteins produce viral enzymes
Replication
Late transcription/translation - viral structure proteins
Virus assembly 
Virus release

Question 7

Virus life cycle

Answer 7

Virus take over much of host cell
All viruses encode unique proteins vital for viral replication and infectivity
These unique proteins are targets for molecular inhibition

Question 8

DNA to DNA requirements

Answer 8

Euk

Dna viruses

Question 9

DNA to RNA

Answer 9

Euk

DNA viruses

Question 10

RNA to RNA

Answer 10

RNA viruses

Question 11

RNA to DNA

Answer 11

Retroviruses (HIV)

Hep B

Question 12

What is azidothymidine?

Answer 12

AZT
Developed in 1965 as anticancer drug
In 1985 found to inhibit HIV replication
Nucleoside reverse transcriptase factor

Question 13

What does NRTI stand for?

Answer 13

Nucleoside reverse transcriptase inhibitors

Question 14

Types of NRTIs

Answer 14

Pyrimidine analogues

Purine analogues

Question 15

E.g. of pyrimidine analogues

Answer 15

Pyr:
Thymidine - zidovudine
Cytosine - lamivudine

Pur:
A & G - abacavir, tenofovir

Question 16

E.g. of newer HIV drugs

Answer 16

Non-nucleotide reverse transcription inhibitors (NNRTI)
Protease inhibitors
Fusion inhibitors - enfuviritide (T20)
Integrase inhibitors - raltegravir
Chemokine receptor antagonists - maraviroc

Question 17

To overcome resistance we have to use which type of therapy

Answer 17

Highly active antiretroviral therapy (HAART)

Question 18

What is involved in HAART?

Answer 18

2 NRTIs + NNRTI
2 NRTIs + boosted PI
Started when CD4 falls
Switches off viral replication
Take forever
Suppression occurs after 10 years

Question 19

HIV cure

Answer 19

HIV suppressed on antivirals
Existing CD4 lymphocytes destroyed by conditioning
Stem cells reconstituted with HLA-matched but delta 32 homozygous allogenieic donor
Antiviral therapy stopped following transplant
Remained HIV negative (by PCR)

Question 20

Hep C virus cures

Answer 20

Interferons and ribavirin cure rates of 40-90% depending on viral genotype
Last 3 years have increasing number of directly acting antivirals against various viral proteins
We now have 90% interferon free regimens for all strains

Question 21

Aciclovir

Answer 21

For Rx (prescription) of Herpes simplex virus (HSV) and Varicella zoster virus (VZV)

Question 22

Ganciclovir

Answer 22

Cytomegalovirus (CMV)

Question 23

Oseltamivir and Zanamavir

Answer 23

Neuraminidase inhibitors

Influenza

Question 24

Ribavirin

Answer 24

Hep C and RSV

Question 25

Interferons

Answer 25

Hep C and Hep B