Anti-virals

Question 1

describe the structure of viruses

Answer 1

• genetic material = RNA/DNA
• capside around genetic material
• some viruses have lipid envelope that is decorated by envelope proteins

Question 2

what do Hep B and C have a tropism for?

Answer 2

liver hepatocytes

Question 3

is Hep B curable? what does this mean for treatment?

Answer 3

• not curable
• all you can do is contain viral replication
• transform it into a chronic disease that is less likely to cause cirrhosis/ liver failure/ cancer

Question 4

at what point do you start Hep B/C treatment?

Answer 4

• a lot of people can clear Hep B/C before they get chronic infection
• infected person should be left for 6 months to see if their immune system will clear it
• if not, need treatment

Question 5

what is the difference between a nucleoside and a nucleotide?

Answer 5

• nucleoside = base and sugar

- nucleotide = base + sugar + phosphate

Question 6

what is the treatment for Hep B?

Answer 6

• Tenofovir = nucleotide analogue, reverse transcriptase inhibitor
• competes w/ endogenous deoxynucleotides that would be used to make up DNA
• block synthesis and generation of more DNA

Question 7

what is the treatment for Hep C?

Answer 7

• Ribavarin and peginterferon alpha

- Boceprivir

Question 8

how do ribavarin and peginterferon alpha work?

Answer 8

compete with endogenous nucleosides, prevents synthesis of RNA

Question 9

how does Boceprivir work?

Answer 9

• protease inhibitor
• effective against Hep C genotype 1 (most common)
• once viral genome has been replicated, certain proteins need to be cleaved to form full virus
• if these are blocked, correct components are not produced

Question 10

describe the attachment and entry into HIV life cycle

Answer 10

• viral membrane proteins interact w/ leukocyte membrane receptors
• leads to viral capsid endocytosis
• HIV GP120 attached to CD4 receptor on T lymphocytes
• GP120 also binds to either CCR5 or CXCR4
• GP41 then penetrates host cell membrane and viral capsid enters

Question 11

describe the replication and integration in HIV life cycle

Answer 11

• within cytoplasm, there is reverse transcriptase
• converts RNA –> DNA
• DNA transported into nucleus, integrated into host DNA

Question 12

describe assembly and release in HIV life cycle

Answer 12

• host cell machinery used to produce copies of viral RNA and essential proteins
• assembled to form new virus particles and mature virions are released

Question 13

name 2 HIV entry inhibitors and how they work

Answer 13

• enfuvirtide: binds to GP41 on HIV and blocks fusion of virus with host cell membrane
• Maraviroc: blocks CCR5 receptor

Question 14

what is the significance of having a polymorphism in CCR5 receptor?

Answer 14

HIV can infect them but it can’t enter their cells

Question 15

what is reverse transcriptase?

Answer 15

• Viral RNA converted to double stranded DNA by reverse transcriptase

Question 16

what do nucleotide/ nucleoside reverse transcriptase inhibitors do?

Answer 16

• Compete with endogenous deoxynucleotides/deoxynucleosides

- inhibit action of reverse transcriptase

Question 17

Give an example of a nucleotide and a nucleoside reverse transcriptase inhibitor

Answer 17

Nucleoside = Zidovudine
Nucleotide = Tenofovir

Question 18

how do non-nucleotide reverse transcriptase inhibitors work?

Answer 18

• Not incorporated into DNA
• Bind to reverse transcriptase
• Cause change in shape of enzyme –> block HIV replication
• E.g. Efavirenz

Question 19

what is the MoA of HIV integrase inhibitors?

Answer 19

• Viral integrase inserts viral DNA into host DNA

- Integrase inhibitor = Raltegravir

Question 20

what happens once the viral RNA has been replicated?

Answer 20

• Capsid produced
• Virus needs to produce some other components to be synthesised to make it complete virus that can infect other cells
• Gag gene encodes ALL viral structural proteins

Question 21

what does HIV protease do?

Answer 21

• cleaves Gag precursor proteins

- releasing proteins that go on to make up complete virus

Question 22

name a HIV protease inhibitor. what is it used with?

Answer 22

• Saquinavir = 1st gen protease inhibitor, low bioavailability so not very good drug
• Low dose ritonavir = reduces metabolism of protease inhibitor (saquinavir)  allows squinavir to reach therapeutic concentrations

Question 23

describe the structure of the Herpes Simplex Virus

Answer 23

• dsDNA virus

- surrounded by tegument and enclosed in lipid bilayer

Question 24

what is the tropisms of HSV?

Answer 24

• HSV1 = cold sores

- HSV2 = genital herpes

Question 25

what is the treatment of HSV?

Answer 25

• acyclovir: nucleoside analogue

- very specific drug, one phosphorylation steps requires viral kinases

Question 26

describe the structure of influenza

Answer 26

• Multipartitie single stranded RNA virus

- Envelope protein neuraminidase important in release of virus into host cell

Question 27

what is the tropism of influenza?

Answer 27

• nose
• throat
• bronchi

Question 28

what drug can be used in influenza treatment?

Answer 28

• Oseltamivir: neuraminidase inhibitor

- Approved for treatment of influenza A and B and prevention of influenza