3: Anti-viral Agents

Question 1

HIV Life cycle

Answer 1

1. gp120 receptor on HIV binds to CD4, then co-receptor CCR5 or CXCR4
2. entry by fusion
3. capsid falls away, exposing genome
4. reverse transcription; RNA–> dsDNA; integrase to enter host DNA
5. host makes viral proteins
6. budding to release virion

Question 2

Viral life cycle

Answer 2

Attachment (specific proteins or glycoproteins = virus receptors) and entry
capsid falls away, exposing genome
make early (regulatory) and late (structural) proteins, making virion
budding or cytolysis

Question 3

Influenza Life cycle

Answer 3

1. attachment (haemagglutinin - spike protein, binds to virus receptors on cells), entry by endocytosis
2. capsid falls away, exposing 8 segments of -ve sense RNA genome
3. mRNA made using RNA-dependent RNA polymerase
4. Viral proteins made using host ribosomes
5. Cytolytic release of virion using neuraminidase

Question 4

What methods are used for viral diagnostics

Answer 4

PCR
ELISA
Serology

Question 5

Things to consider when developing anti-viral drugs

Answer 5

Cost
Administration- easy to administer?
Safety - even more than efficacy
Strains - does it deal with all strains?

Question 6

3 main targets for anti-viral drugs

Answer 6

Viral enzymes
Nucleosides
Specific viral factors

Question 7

Acyclovir - antiviral drug

Answer 7

Nucleoside analogue
lacks 3’OH group –> chain termination
specific to HSV (herpes simplex virus) :
only HSV has herpes viral thymidine kinase
phosphorylates ACV -> AVMP
ACVMP->ACVTP by cellular enzymes

Question 8

Remdesevir

Answer 8

Adenosine analogue
chain termination 3 nucleotides downstream of incorporation by twisting shape of DNA/RNA
Developed for Hep C and Ebola

Question 9

Ideal features of antivirals against influenza

Answer 9

Target unique gene/function
Effective against multiple strains
Easy to administer
Few side effects

Question 10

Admantanes

Answer 10

Cyclic amines
only active against Influenza A
e.g Admantadine, Rimantadine

Question 11

Admantadine

Answer 11

resistant to H3N2
targets M2 ion channel
no protons removed from acidic endosome to core of virus particle
M1 matrix protein and nuclear protein interaction remain intact
virus unable to uncut
no viral genome released into host cell

Question 12

Neuraminidase Inhibitors

Answer 12

Prevent cleavage of sialic acid from host cell membrane
so virus remains attached to host cell
cannot infect other cells

Question 13

3 Neuraminidase Inhibitors

Answer 13

Tamiflu (oseltamivir) - H1N1 resistant, halved risk of death from swine flu if taken within 48h

Zanamivir (Relenza)

Baloxivir - for influenza A&B - inhibits PA subunit of viral polymerase so prevents viral transcription

Question 14

What drugs work against Hepatitis C

Answer 14

Protease inhibitors
Polymerase inhibitors

Question 15

Sustained virological response (SVR)

Answer 15

positive effect of an antiviral drug on reducing the amount of a virus in a patient

Question 16

5 types of HIV Treatments

Answer 16

Protease inhibitors
Co-receptor antagonists
Fusion inhibitors
Nuceleoside reverse transcriptase inhibitors (NRTIs)
Integrase inhibitors

Question 17

3 HIV Treatments

Answer 17

HAART - highly active antiviral anti-retroviral therapy ; many pills narrowed down to one

PrEP - antivirals taken despite infection not being present, Trivada

AZT - azedothymadine
nucleoside analogue

Question 18

Passive immunotherapy

Answer 18

antibodies taken from recovered individual, or produced from immortalized B cells