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Virology FRCPath Part 2 > Antivirals > Flashcards

Antivirals Flashcards

1
Q

What is Pritelivir used to treat?
What is it’s mode of action?

A

HSV-1 and HSV-2
Viral helicase-primase complex inhibitors

Note that Amenamevir has similar mode of action

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2
Q

What is Lencapavir used to treat? What is it’s mode of action?

A

HIV
Capsid inhibitors

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3
Q

What is Letermovir used to treat? What is it’s mode of action?

A

CMV Prophylaxis
Viral DNA terminase complex inhibitor
Resistance gene is UL56

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4
Q

Maribavir

A

CMV
UL97 protein kinase inhibitor. Interferes with ATP binding

Note DDI with tacrolimus

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5
Q

Baloxavir marboxil

A

Influenza A and B
Inhibits viral cap-dependent endonuclease

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6
Q

Oseltamivir

A

Influenza A and B
Neuraminidase inhibitor

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7
Q

Zanamivir

A

Influenza A and B
Neurominidaze inhibitor

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8
Q

Pocapavir

A

Enterovirus / polio
Capsid inhibitor

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9
Q

Favipiravir

A

Influenza, sars cov 2, arenaviruses
? enterovirus ? Nipah ?WNV ?YFV ?Rift valley fever. ??Rabies and Zika
RDRP inhibition

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10
Q

Galidesivir

A

Nucleotide analogue
RNA viruses
?Ebola, Marburg, Zika
I’m GLAD ITS HERE given the viruses it works against

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11
Q

Peramivir

A

Influenza
Neurominidase inhibitor

Peramivir
should not be used in patients with known oseltamivir resistance.Not available in UK. IV one dose, may have place for non-complicated influenza

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12
Q

Ensitrelvir

A

Sars-CoV-2 PEP or treating smell and taste loss post covid-19 infection. SCORPIO-PEP trial
Protease inhibitor

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13
Q

Nelfinavir

A

HIV-1
protease inhibitor

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14
Q

Riamilovir

A

Pandemic influenza
TBE
?Lassa ?Ebola
Inhibits RNA synthesis

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15
Q

Clevudine

A

HBV
Nucleos/tide analogue. Inhibits viral DNA pol

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16
Q

Lagociclovir valactate

A

HBV
Nucleos/tide analogue. Inhibits viral DNA pol

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17
Q

Besifovir

A

HBV
Nucleos/tide analogue. Inhibits viral DNA pol

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18
Q

Myrcludex-B

A

HBV / HDV
Entry inhibitor - binds NTCP

Now called bulevitide

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19
Q

Phenylpropenamides

A

HBV
Inhibits viral encapsidation

PhENylpropENamides

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20
Q

Nitazoxanide

A

HBV
small molecule

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21
Q

Zadaxin

A

HBV
Immunomodulator

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22
Q

Bepirovirsen

A

HBV
Antisense oligonucleotide which targets HBV mRNA

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23
Q

Remdesivir

A

RNA-dependent RNA polymerase(RdRp) inhibitor

Dose is 3 days for “OPD” (200mg loading, followed by 100 then 100), inpatients for treatment get 5-10 days

Has to be started within 10 days, avoid if ALT five times upper limit of normal.

Key trials: PINETREE

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24
Q

Molnuprivir

Acronym MRA

A

Molnupiravir (a prodrug) is a ribonucleoside analogue that increases the number of mutations in viral RNA thus preventing multiplication of the virus

mutagenic ribonucleoside anologue

Remeber: Teenage MUTANT hero turtles

COVID-19 in patients who do not require oxygen supplementation and are at an increased risk of severe COVID-19 infection
for molnupiravir
By mouth
Adult
800 mg twice daily for 5 days, treatment to be started as soon as possible after diagnosis and within 5 days of symptom onset.

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25
Q

Lenecapavir and indication

A

capsid maturation inhibitor
In BHIVA guidelines for

“In those with significant resistance, include at least two and preferably three fully active agents with
at least one active boosted PI (preferably ritonavir- or cobicistat-boosted darunavir) and one agent
with a novel mechanism of action (these may include INSTIs, CCR5 antagonists, molecules targeting
glycoprotein 120 [gp120; fostemsavir], monoclonal antibodies targeting CD4 [ibalizumab], capsid
inhibitors [lenacapavir], the fusion inhibitor T-20 or other investigational agents). “

26
Q

What is the dose of ganciclovir for HHV-6 encephalitis bone HSCT

A

5mg/kg (some studies used higher doses)

27
Q

Describe dosing of foscarnet for CMV

A

Induction followed by maintenence
Induction: 60mg/kg TDS for two to three weeks (or 90 mg/kg every BD)

Maintenance
60 mg/kg daily (same as above but daily rather than TDS), then increased if tolerated to 90–120 mg/kg daily

Note for HSV it is 40mg/kg TDS (no maintenance dose)

28
Q

Key drug interactions with foscarnet

A

Anything nephrotoxic
Pentamidine- causes calcium problems

Note: Women capable of childbearing should use effective contraception methods during Foscavir therapy.

Men treated with Foscavir should not father a child during or up to 6 months after therapy

29
Q

what is the metabolite of aciclovir that can be measured in suspected toxicity

A

9-carboxymethoxymethylguanine (CMMG)

30
Q

What is the treatment regime for herpes B exposure

A

14 days of valaciclovir (1gm TDS), or aciclovir 800mg 5 times a day
- some recommend lifelong treatment
Start ASAP but within 5 days

31
Q

Describe foscarnet dosing regimes for
1) CMV retinitis
2) Resistant HSV

A

1) Induction* followed by maintenance**
*adminisered over two-three weeks, 60mg/kg
**60mg/kg daily increase up to 120 if tolerate

2) 40mg/kg TDS induction for indiction- no recommendations for maintenance

NOTE: first line therapy is PO valgan 900mg BD for 14-21 days + intravitreal foscarnet 2.4mg

32
Q

Treatment options for pregnant person with HIV and CMV disease

A

If eye disease, try limiting to topical foscarnet

Way up risk vs benefit

33
Q

Drug interactions of maribavir

A

Immunosupressants- increased them (see SOLSTICE trial)

34
Q

ST-193

A

Lassa virus and other Arenaviruses (Guanarito, Junin, and Machupo virus)
Fusion inhibitor

Salvage therapy attempt #193 🤣

35
Q

Zaire Ebola monoclonals

A

Atoltivimab/maftivimab/odesivimab (inmazeb)

Ebanga (ansuvimab)

Look up palm trial

36
Q

Palivuzimab

A

Prevention of RSV

37
Q

Niresevimab

A

Prevention of RSV

38
Q

Ibalizumab

A

HIV-1

39
Q

pembriluzimab

A

JC
Checkpoint inhibitor

Adverse effects: pneumonia, anaemia, thrombocytopenia

PeMbriLuzimab

40
Q

Nivolumab

A

JC virus
Checkpoint inhibitor

41
Q

trifluridine uses

A

HSV eye disease
MPox kerititis

42
Q

Tecoviromat

A

Inhibitor of VP37 envelope protein

BD dosing for 14 days

smallpox, monkeypox and cowpox

43
Q

Islatravir

A

HIV
NRTTI (nucleoside reverse transcriptase translocation inhibitor)

Initially concern as it reduced CD4 count but now can be used in lower doses

44
Q

Enfurvirtide

A

HIV fusion inhibitor

45
Q

Lenacapavir

A

Capsid inhibtor

46
Q

Cidofovir action

A

Nucleoside analogue, inhibits DNA polymerase

47
Q

Foscarnet mechanism

A

Pyrophosphate analog, inhibits DNA polymerase

48
Q

Cidofovir SE

A

Renal failure
Leukopenia
Anterior uveitis
Hypospermia

49
Q

What is experimental antiviral GHP-88309 used for?

A

Measles antiviral.
Reduces viraemia, mortality and prevents lymphopenia and immune amnesia in animal model.
“Therapeutic mitigation of measles-like immune amnesia and exacerbated disease after prior respiratory virus infections in ferrets” Cox et al 2024, Nature

50
Q

Bulevirtide

A

Inhibits NTCP (Bulevirtide is a sodium-bile acid co-transporter inhibitor)

Delta enters hepatocytes via Enters via NTCP, however there is also spread between hepatocytes, which BLV does not block

BLV blocks the formation of both covalently closed circular DNA and HDV replicative intermediates and its continuous administration decreases the fraction of infected cells by blocking the HBV-mediated spread of HDV.149, 150, 151 However, during BLV treatment, intrahepatic HDV spreading due to the HBV/NTCP-independent, cell division-mediated mechanism persists, antagonising the eradication of HDV infection

51
Q

Staging and Treatment of KS

A

Staging-
Uses TIS (Tissue, Immune system, Systemic illness)

https://www.cancer.org/cancer/types/kaposi-sarcoma/detection-diagnosis-staging/staging.html

Treatment: ART
If T1 disease is present, or lesions not regressing with ART, chemotherapy can be considered
– Doxorubicin is 1st line

52
Q

uses of interferon lamda (2)

A

1 COVID

predominantly vaccinated population infected with various SARS-CoV-2 variants of concern, showed the efficacy of a single subcutaneous dose of pegylated interferon lambda administered within 7 days after the onset of symptoms (mean, 3 days). This regimen resulted in a greater than 50% reduction in the risk of a primary-outcome event. Our trial findings were consistent across the SARS-CoV-2 variants of concern and across multiple subgroups according to vaccination status.

2) HDV

(expand)

53
Q

Amenamevir

A

helicase primase inhibitor

(same as pritelivir)

Action against HSV and VZV

54
Q

Filociclovir

A

Nucleoside analogue

Action against CMV ?adeno

55
Q

Pleoconaril

A

viral capsid—function inhibitor
Action against picornoviruses

56
Q

Drugs that inhibit capsids

A

Pleoconaril- capisd function inhibitor (picorno)
Baloxavir - cap-dependent endonuclease (influenza)
Lenacapavir- HIV, capsid maturation inhibitor

57
Q

Tecoviromat

A

inhibits viral protein p37, encoded by the F13 gene of the variola virus (15). This protein is highly conserved in orthopoxviruses, allowing tecovirimat to have in vitro activity against several orthopoxviruses, including vaccinia, variola, cowpox, and monkeypox viruses (15, 16). The p37 protein is involved in the final steps of maturation of the virus and is required for the intracellular mature virus (IMV) to further envelope without a double membrane layer to form intracellular enveloped virus (IEV). IEV then fuses with the cytoplasmic membrane to release virions to disseminate from the site of infection (15). The p37 protein is specific to the orthopoxvirus family, making tecovirimat highly selective with the inability to inhibit replication of other classes of viruses, including herpesviruses

58
Q

Treatment of mpox

A

Tecoviomat:

Indications

59
Q

Clesrovimab

A

RSV monoclonal (in phase three)

60
Q

Nirmatrelvir/ritonavir

A

Inhibits 3C like protease (inhibits Mpro)
Needs to be started within 5 days of symptoms onset

Trial is EPIC HR

Virology FRCPath Part 2 (24 decks)

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