Antivirals Flashcards
What viruses does tecovirimat have activity against and what is the target?
All orthopoxvirus - it target and inhibits orthopox VP37, inhibiting viral egress
Which antivirals can be used against smallpox?
Tecovirimat and brincidofovir (or cidofovir)
What is trifluradine used for?
Eye drops for HSV and vaccinia keratitis. It is a nucleoside analogue.
What is brivudine?
Nucleoside analogue license ld to treat shingles, but not in UK
Is cidofovir virostatic or virocidal?
Virostatic - immune response required to clear infection
What is the main amantadine resistance mutation in influenza A?
S31N
What antivirals are available for influenza? Name 8 antivirals
M2 ion channels
Amantadine Rimantidine
Neuraminidase inhibitors
Oseltamivir Zanamavir Peramivir Laninamivir
Polymerase inhibitors
Baloxavir Favipirivir
What is the mechanism of action of adamantanes?
What virus is this active against?
Blocks hydrogen ion influx through M2 ion channel, preventing viral uncoating
Active against flu A but not flu B
What is the mechanism of action of the neuraminidase inhibitors?
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
Name two influenza polymerase inhibitors and their targets
Baloxivir - PA - inhibits cap-dependent endonuclease
Favipirivir - PB1
What are the most common resistance mutations to oseltamivir and zanamavir?
Oseltamivir
H1N1 - H275Y
H3N2 - E119V and R292K
Zanamivir
H1N1/H3N2 - Q136K
H3N2 - R292K
What administration routes are 1) oseltamivir, 2) zanamivir, 3) peramivir, 4) baloxivir
1) oral
2) inhaled and IV
3) IV infusion
4) oral
What is the administrative route, dose regime and most common resistance mutation for baloxivir?
Oral
Single dose
I38T/M/F (more common in H3N2)
Nucleos(t)ide analogues with activity against HSV?
Nucleoside
-Acivlovir
-Ganciclovir (less activity but still some)
-Famciclovir (acetylated
penciclovir)
Nucelotide
- Cidofovir
- Adefovir
Non nucleos(t)ide inhibitors with activity against HSV?
Foscarnet - pyrophosphate analogue
Pritelivir - Helicase/Primase inhibitor
Amenamevir - (not in use in the UK - approved in Japan)
HSV gene mutations conferring resistance to aciclovir and result of mutation?
UL23 - TK (95%)
UL30 - DNA pol (5%)
Relevant gene mutations in HSV
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
Name two helicase-primase inhibitors with activity against HSV
Pritelivir
Amenamevir
Can tecovirimat be used in pregnancy?
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
Mechanism of action of pocapavir and limitation of treatment
Enterovirus specific capsid inhibitor - blocks viral uncoating and RNA release
Difficult to procure and can only be used for 2 weeks in total
Name two IL-6 receptor antagonists for use in COVID infection. When would you initiate these? What should you be cautious of?
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.
Name the JAK-inhibitor used for treating COVID. When would you use this and what are the contraindications?
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
When would you use nirmatrelvir and ritonavir (paxlovid)?
In patients presenting within 5 days
Not requiring oxygen but are high risk of severe disease
What window do you need with treat flu within for the following:
- Oseltamivir
- Zanamavir in adults
- Zanamavir in children
- IV Zanamavir
- Within 48 h (up to 5 days off-label)
- Within 48 h
- Within 36 h
- Within 6 days
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)
In what age is zanamivir licensed? Dose and duration of treatment?
Over 5 years
10 mg BD 5 days
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
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
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
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
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
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
What is Tabelecleucel?
Off the shelf EBV specific cytotoxic T cells for use in relapsing and refractory EBV+ PTLD
What type of drug is ribavirin?
Nucleoside (guanosine) analogue
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
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
What is the treatment for acute disseminated encephalomyelitis?
Corticosteroids, IVIG and plasma exchange
What is posoleucel?
Off the shelf CTL for 6 viruses (adeno, BK, JC, CMV, EBV, HHV-6)
Phase III trails have been cancelled though :(
What is lonafarnib?
Oral prenylation inhibitor being investigated for HDV treatment (ritonavir boosted +/- IFN)
What is Inmazeb and Ebanga?
Monoclonals to Ebola Zaire
Inmazeb - REGN-EB3
Ebanga - mAb114
Treatment/prophylaxis of PCP?
Co-trimoxazole
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
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
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
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
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
What age and weight is maribavir licensed?
Licenced for >12 y and BW >35 kg (although EMA >18 y)
What resistance mutations cause maribavir resistance?
T409M and H411Y and C480F in UL97
Also resistance mutations in UL27
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)
What is penciclovir and famciclovir?
Penciclovir is a acyclic guanine derivative = short chain terminator
Famciclovir is its oral pro drug
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
What is imiquimod?
TLR-7/8 agonist that stimulates cytokine production to stimulate Th1 response
Used in aciclovir resistant genital herpes
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
What is IC50?
IC50 (50% inhibitory concentration) concentration of drug that reduces the plaque number by 50% compared to no antiviral
