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Antivirals Flashcards

1
Q

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

A

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

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2
Q

Which antivirals can be used against smallpox?

A

Tecovirimat and brincidofovir (or cidofovir)

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3
Q

What is trifluradine used for?

A

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

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4
Q

What is brivudine?

A

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

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5
Q

Is cidofovir virostatic or virocidal?

A

Virostatic - immune response required to clear infection

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6
Q

What is the main amantadine resistance mutation in influenza A?

A

S31N

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7
Q

What antivirals are available for influenza? Name 8 antivirals

A

M2 ion channels

Amantadine
Rimantidine

Neuraminidase inhibitors

  Oseltamivir 
  Zanamavir
  Peramivir
  Laninamivir

Polymerase inhibitors

 Baloxavir 
 Favipirivir
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8
Q

What is the mechanism of action of adamantanes?

What virus is this active against?

A

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

Active against flu A but not flu B

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9
Q

What is the mechanism of action of the neuraminidase inhibitors?

A

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

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10
Q

Name two influenza polymerase inhibitors and their targets

A

Baloxivir - PA - inhibits cap-dependent endonuclease

Favipirivir - PB1

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11
Q

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

A

Oseltamivir

H1N1 - H275Y
H3N2 - E119V and R292K

Zanamivir

H1N1/H3N2 - Q136K
H3N2 - R292K

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12
Q

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

A

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

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13
Q

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

A

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

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14
Q

Nucleos(t)ide analogues with activity against HSV?

A

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

Nucelotide
- Cidofovir
- Adefovir

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15
Q

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

A

Foscarnet - pyrophosphate analogue

Pritelivir - Helicase/Primase inhibitor

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

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16
Q

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

A

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

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17
Q

Relevant gene mutations in HSV

A

UL 23 - TK - confers ACV resistance
UL30 - DNA pol - Multi class resistance possible - ACV, FOS, CID
UL5/UL52/UL8 - DNA helicase/primase - possible pritelivir resistance

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18
Q

Name two helicase-primase inhibitors with activity against HSV

A

Pritelivir

Amenamevir

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19
Q

Can tecovirimat be used in pregnancy?

A

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

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20
Q

Mechanism of action of pocapavir and limitation of treatment

A

Enterovirus specific capsid inhibitor - blocks viral uncoating and RNA release

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

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21
Q

Name two IL-6 receptor antagonists for use in COVID infection. When would you initiate these? What should you be cautious of?

A

Tocilizumab and Sarilumab

When patients are on oxygen and corticosteroids

Sarilumab is not licensed but can be used if Tocilizumab unavailable

Potent immunosuppressors so patients are risk of opportunistic infection. Use in immunosuppressed patients requires caution.

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22
Q

Name the JAK-inhibitor used for treating COVID. When would you use this and what are the contraindications?

A

Baricitinib

Age 2+ for patients on oxygen and corticosteroids AND with no evidence of another infection that might be made worse

Can be added to toculizumab or used instead if tocilizumab if it can not be tolerated

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23
Q

When would you use nirmatrelvir and ritonavir (paxlovid)?

A

In patients presenting within 5 days
Not requiring oxygen but are high risk of severe disease

24
Q

What window do you need with treat flu within for the following:

  1. Oseltamivir
  2. Zanamavir in adults
  3. Zanamavir in children
  4. IV Zanamavir
A
  1. Within 48 h (up to 5 days off-label)
  2. Within 48 h
  3. Within 36 h
  4. Within 6 days
25
In which situations would you consider using IV zanamivir to treat influenza?
Severely immunosuppressed patients with complicated flu (in H1 season) who are unable to use diskhaler Severely immunosuppressed patients with severe complications such as multi organ failure (in H1 season)
26
In what age is zanamivir licensed? Dose and duration of treatment?
Over 5 years 10 mg BD 5 days
27
Do zanamivir and oseltamivir require dose adjustment for 1) renal dysfunction 2) hepatic dysfunction
1) Oseltamivir = yes, inhaled zanamavir = no, IV zanamavir = yes 2) Oseltamivir = no, inhaled zanamavir = no, IV zanamavir = yes
28
What class of drug is nirmatrelvir? What drug is added to this to treat COVID? And who would you treat with this regimen?
Protease inhibitor Ritonavir COVID patients without oxygen requirements, who are at high risk of severe disease
29
What class of drug is remdesivir? When would you use it for COVID treatment? What is administration route?
RNA polymerase inhibitors (adenosine nucleotide prodrug) Patients at high risk of severe disease IV
30
What is the mechanism of action of molnupiravir? When would you use it in COVID treatment? What is administration route?
Nucleoside analogue which causes mutagenesis in the viral RNA Adults at high risk of disease, within 5 days of symptoms, who do not require O2 (can be used interchangeably with paxlovid) Oral
31
What class of drug is tocilizumab? What other drug is the same class can be used instead? What specifically are patients at risk of?
IL6 receptor antagonist Sarilumab Potent immunosuppressant so patients are at risk of opportunistic infection
32
What class of drug is Baricitinib? When specifically should this not be used?
Janus Kinase (JAK) inhibitors Cannot be used if patients have evidence of any other infection that could be made worse with treatment
33
What is Tabelecleucel?
Off the shelf EBV specific cytotoxic T cells for use in relapsing and refractory EBV+ PTLD
34
What type of drug is ribavirin?
Nucleoside (guanosine) analogue
35
What is rituximab? How long does the induced B cell suppression last for? What are the implications of this?
Anti- CD20 MAb 2-6 months At risk of opportunistic infections and unable to have vaccination during this time due to likely poorer responses
36
What is CAR-T therapy and what implications does it have in virology?
Chimeric antigen receptor T cell therapy Patients T cells are modified to include a receptor to recognise and kill cancer cells Can be used in refractory B cell ALL, DLBCL, B cell and mantel cell lymphoma Patients are severely immunosuppressed and can be at risk of viral reactivation and opportunistic infection
37
What is the treatment for acute disseminated encephalomyelitis?
Corticosteroids, IVIG and plasma exchange
38
What is posoleucel?
Off the shelf CTL for 6 viruses (adeno, BK, JC, CMV, EBV, HHV-6) Phase III trails have been cancelled though :(
39
What is lonafarnib?
Oral prenylation inhibitor being investigated for HDV treatment (ritonavir boosted +/- IFN)
40
What is Inmazeb and Ebanga?
Monoclonals to Ebola Zaire Inmazeb - REGN-EB3 Ebanga - mAb114
41
Treatment/prophylaxis of PCP?
Co-trimoxazole
42
43
Mechanism of action, administration route and side effects of ganciclovir
Nucleoside (guanosine) analogue. Activated into ganciclovir triphosphate, initially by UL97 and then cellular kinases. GCV-triphosphate competitively inhibits incorporation of deoxyguanosine triphosphate. Slows viral replication. IV (valganciclovir is oral) Bone marrow suppression
44
Mechanism of action, administration route and side effects of foscarnet
Pyrophosphate analogue. Non competitive inhibitor of viral DNA by binding DNA polymerase directly. Does not require phosphorylation IV Nephrotoxicity. Hypocalcaemia, electrolyte imbalance (can cause seizures), genital ulceration
45
Mechanism of action, administration route and side effects of cidofovir
Acyclic nucleotide (cytodine) analogue. After phosphorylation by cellular kinases, cidofovir diphosphate inhibits DNA polymerase by competitive inhibition of viral DNA polymerase disrupting elongation IV Nephrotoxicity - requires probenecid and hyper hydration
46
Mechanism of action, administration route and side effects of letermovir
Inhibits DNA synthesis at late stage by targeting UL56 subunit of the terminase enzyme complex Oral Low/no side effects
47
Mechanism of action, administration route and side effects of maribavir
Inhibition of CMV UL97 by competing with ATP. Does not require intracellular phosphorylation. Oral Taste and gastrointestinal disturbances
48
What age and weight is maribavir licensed?
Licenced for >12 y and BW >35 kg (although EMA >18 y)
49
What resistance mutations cause maribavir resistance?
T409M and H411Y and C480F in UL97 Also resistance mutations in UL27
50
Mechanism of action, administration route and side effects of aciclovir
Nucleoside (guanosine) analogue. Selective phosphorylation only in virally infected cells. First phosphorylation step by TK, two further steps by cellular kinases. ACV-triphosphate can be incorporated into DNA causing chain termination. IV or oral Few side effects (mostly the usual)
51
What is penciclovir and famciclovir?
Penciclovir is a acyclic guanine derivative = short chain terminator Famciclovir is its oral pro drug
52
Mechanism of action and administration route of pritelevir
Helicase primase inhibitor. The helicase-primase complex is composed of 3 proteins encoded by the UL5 (helicase), UL8 (scaffold region), and UL52 (primase) Single oral tablet daily
53
What is imiquimod?
TLR-7/8 agonist that stimulates cytokine production to stimulate Th1 response Used in aciclovir resistant genital herpes
54
Options for HSCT patients with aciclovir resistant HSV
Consider high dose aciclovir (10 mg/kg TDS) First line = foscarnet, alternative = cidofovir If not working, can try high dose IV aciclovir 30-45 mg/kg +/- foscarnet Topical treatments can be tried for those who are at risk of toxicities from systemic agents
55
What is IC50?
IC50 (50% inhibitory concentration) concentration of drug that reduces the plaque number by 50% compared to no antiviral

Part 2 Revision (57 decks)

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