Antivirals

Question 1

What viruses does tecovirimat have activity against and what is the target?

Answer 1

All orthopoxvirus - it target and inhibits orthopox VP37, inhibiting viral egress

Question 2

Which antivirals can be used against smallpox?

Answer 2

Tecovirimat and brincidofovir (or cidofovir)

Question 3

What is trifluradine used for?

Answer 3

Eye drops for HSV and vaccinia keratitis. It is a nucleoside analogue.

Question 4

What is brivudine?

Answer 4

Nucleoside analogue license ld to treat shingles, but not in UK

Question 5

Is cidofovir virostatic or virocidal?

Answer 5

Virostatic - immune response required to blest infection

Question 6

Is cidofovir virostatic or virocidal?

Answer 6

Virostatic - immune response required to clear infection

Question 7

What is the main amantadine resistance mutation in influenza A?

Answer 7

S31N

Question 8

What antivirals are available for influenza? Name 8 antivirals

Answer 8

M2 ion channels

Amantadine
Rimantidine

Neuraminidase inhibitors

  Oseltamivir 
  Zanamavir
  Peramivir
  Laninamivir

Polymerase inhibitors

 Balixavir
 Favipirivir

Question 9

What is the mechanism of action of adamantanes?

What virus is this active against?

Answer 9

Blocks hydrogen ion influx through M2 ion channel, preventing viral uncoating

Active against flu A but not flu B

Question 10

What is the mechanism of action of the neuraminidase inhibitors?

Answer 10

Analogs of sialic acid, bind the cleavage site of NA so it can’t cleave HA from sialic acid and therefore virus can not be released

Question 11

Name two influenza polymerase inhibitors and their targets

Answer 11

Baloxivir - PA - inhibits cap-dependent endonuclease

Favipirivir - PB1

Question 12

What are the most common resistance mutations to oseltamivir and zanamavir?

Answer 12

Oseltamivir

H1N1 - H275Y
H3N2 - E119V and R292K

Zanamivir

H1N1/H3N2 - Q136K
H3N2 - R292K

Question 13

What administration routes are 1) oseltamivir, 2) zanamivir, 3) peramivir, 4) baloxivir

Answer 13

1) oral
2) inhaled and IV
3) IV infusion
4) oral

Question 14

What is the administrative route, dose regime and most common resistance mutation for baloxivir?

Answer 14

Oral
Single dose
I38T/M/F (more common in H3N2)

Question 15

Nucleos(t)ide analogues with activity against HSV?

Answer 15

Nucleoside
-Acivlovir
-Ganciclovir (less activity but still some)
-Famciclovir (acetylated
penciclovir)

Nucelotide
- Cidofovir
- Adefovir

Question 16

Non nucleos(t)ide inhibitors with activity against HSV?

Answer 16

Foscarnet - pyrophosphate analogue

Pritelivir - Helicase/Primase inhibitor

Amenamevir - (not in use in the UK - approved in Japan)

Question 17

Locations of gene mutations conferring resistance to aciclovir and result of mutation?

Answer 17

UL23 - TK (95%)
UL30 - DNA pol (5%)

Question 18

Relevant gene mutations in HSV

Answer 18

UL 23 - TK - confers ACV resistance
UL30 - DNA pol - Multi class resistance possible - ACV, FOS, CID
UL5 - DNA helicase/primase - possible pritelivir resistance

Question 19

Name two helicase-primase inhibitors with activity against HSV

Answer 19

Pritelivir

Amenamevir

Question 20

Can tecovirimat be used in pregnancy?

Answer 20

Not licensed, should only be used if severe disease, breastfeeding contraindicated.

Vertical transmission is possible (highest risk in first trimester) baby to be tested at birth (throat, urine, blood) if negative vaccinate baby

Question 21

Mechanism of action of pocapavir and limitation of treatment

Answer 21

Enterovirus specific capsid inhibitor - blocks viral uncoating and RNA release

Difficult to procure and can only be used for 2 weeks in total