Antivirals Flashcards
What is Pritelivir used to treat?
What is it’s mode of action?
HSV-1 and HSV-2
Viral helicase-primase complex inhibitors
Note that Amenamevir has similar mode of action
What is Lencapavir used to treat? What is it’s mode of action?
HIV
Capsid inhibitors
What is Letermovir used to treat? What is it’s mode of action?
CMV Prophylaxis
Viral DNA terminase complex inhibitor
Resistance gene is UL56
Maribavir
CMV
UL97 protein kinase inhibitor. Interferes with ATP binding
Note DDI with tacrolimus
Baloxavir marboxil
Influenza A and B
Inhibits viral cap-dependent endonuclease
Oseltamivir
Influenza A and B
Neuraminidase inhibitor
Zanamivir
Influenza A and B
Neurominidaze inhibitor
Pocapavir
Enterovirus / polio
Capsid inhibitor
Favipiravir
Influenza, sars cov 2, arenaviruses
? enterovirus ? Nipah ?WNV ?YFV ?Rift valley fever. ??Rabies and Zika
RDRP inhibition
Galidesivir
Nucleotide analogue
RNA viruses
?Ebola, Marburg, Zika
I’m GLAD ITS HERE given the viruses it works against
Peramivir
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
Ensitrelvir
Sars-CoV-2 PEP or treating smell and taste loss post covid-19 infection. SCORPIO-PEP trial
Protease inhibitor
Nelfinavir
HIV-1
protease inhibitor
Riamilovir
Pandemic influenza
TBE
?Lassa ?Ebola
Inhibits RNA synthesis
Clevudine
HBV
Nucleos/tide analogue. Inhibits viral DNA pol
Lagociclovir valactate
HBV
Nucleos/tide analogue. Inhibits viral DNA pol
Besifovir
HBV
Nucleos/tide analogue. Inhibits viral DNA pol
Myrcludex-B
HBV / HDV
Entry inhibitor - binds NTCP
Now called bulevitide
Phenylpropenamides
HBV
Inhibits viral encapsidation
PhENylpropENamides
Nitazoxanide
HBV
small molecule
Zadaxin
HBV
Immunomodulator
Bepirovirsen
HBV
Antisense oligonucleotide which targets HBV mRNA
Remdesivir
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
Molnuprivir
Acronym MRA
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.
Lenecapavir and indication
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). “
What is the dose of ganciclovir for HHV-6 encephalitis bone HSCT
5mg/kg (some studies used higher doses)
Describe dosing of foscarnet for CMV
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)
Key drug interactions with foscarnet
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
what is the metabolite of aciclovir that can be measured in suspected toxicity
9-carboxymethoxymethylguanine (CMMG)
What is the treatment regime for herpes B exposure
14 days of valaciclovir (1gm TDS), or aciclovir 800mg 5 times a day
- some recommend lifelong treatment
Start ASAP but within 5 days
Describe foscarnet dosing regimes for
1) CMV retinitis
2) Resistant HSV
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
Treatment options for pregnant person with HIV and CMV disease
If eye disease, try limiting to topical foscarnet
Way up risk vs benefit
Drug interactions of maribavir
Immunosupressants- increased them (see SOLSTICE trial)
ST-193
Lassa virus and other Arenaviruses (Guanarito, Junin, and Machupo virus)
Fusion inhibitor
Salvage therapy attempt #193 🤣
Zaire Ebola monoclonals
Atoltivimab/maftivimab/odesivimab (inmazeb)
Ebanga (ansuvimab)
Look up palm trial
Palivuzimab
Prevention of RSV
Niresevimab
Prevention of RSV
Ibalizumab
HIV-1
pembriluzimab
JC
Checkpoint inhibitor
Adverse effects: pneumonia, anaemia, thrombocytopenia
PeMbriLuzimab
Nivolumab
JC virus
Checkpoint inhibitor
trifluridine uses
HSV eye disease
MPox kerititis
Tecoviromat
Inhibitor of VP37 envelope protein
BD dosing for 14 days
smallpox, monkeypox and cowpox
Islatravir
HIV
NRTTI (nucleoside reverse transcriptase translocation inhibitor)
Initially concern as it reduced CD4 count but now can be used in lower doses
Enfurvirtide
HIV fusion inhibitor
binds to GP41
Lenacapavir
Capsid inhibtor
Cidofovir action
Nucleoside analogue, inhibits DNA polymerase
Foscarnet mechanism
Pyrophosphate analog, inhibits DNA polymerase
Cidofovir SE
Renal failure
Leukopenia
Anterior uveitis
Hypospermia
What is experimental antiviral GHP-88309 used for?
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
Bulevirtide
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
Staging and Treatment of KS
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
uses of interferon lamda (2)
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)
Amenamevir
helicase primase inhibitor
(same as pritelivir)
Action against HSV and VZV
Filociclovir
Nucleoside analogue
Action against CMV ?adeno
Pleoconaril
viral capsid—function inhibitor
Action against picornoviruses
Drugs that inhibit capsids
Pleoconaril- capisd function inhibitor (picorno)
Baloxavir - cap-dependent endonuclease (influenza)
Lenacapavir- HIV, capsid maturation inhibitor
Tecoviromat
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
Treatment of mpox
Tecoviomat:
Indications
Clesrovimab
RSV monoclonal (in phase three)
Nirmatrelvir/ritonavir
Inhibits 3C like protease (inhibits Mpro)
Needs to be started within 5 days of symptoms onset
Trial is EPIC HR
