17. Anti-viral Chemotherapy Flashcards
What is the virus particle?
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Has lipoprotein envelope
Core proteins (capsid)
RNA or DNA core
Surface proteins
What are viruses?
Small obligate intracellular parasites
Contain nucleic acid core surrounded by a protein capsid; with an envelope
Attach to host cell receptors then enter cell by endocytosis or penetration
Use hosts mechanisms of replication cause viruses can’t themselves
Assemble virions within the host cell, released during cell lysis (nonenveloped viruses) or budding (enveloped viruses)
Slides 4-7
What are viral infections?
Can’t be lytic (destroy host), latent (no signs or symptoms for long time), chronic (when virus buds from host cell, infection can be chronic)
Can be awaited from humans, animals or environment; through direct contacts or environmental routes
Characterized by incubation period
Can spread to other tissues
Slides 8-10
What are the 8 things to do to treat viral infections?
- Block viral attachment to cells
- Block in coating of virus
- Inhibit viral DNA/RNA synthesis
- Inhibit viral protein synthesis
- Inhibit specific viral enzymes
- Inhibit viral assembly
- Inhibit viral release
- Stimulate host immune system
Slides 9-10
How do you treat respiratory virus infections?
Treatments exist for influenza types A and B, and respiratory syncytial virus (RSV)
Immunization against influenza virus is the preferred approach (annual flu shot)
Slides 12-13
What are neuraminidase inhibitors?
3 drugs
Oseltamivir
Zanamivir
Peramivir
Neuraminidase removes sialic acid receptors from viral particles and from cell surface, preventing self aggregation and gluing to infected cell surface
These 3 drugs inhibit neuraminidase of influenza A and B viruses, and prevent release of new virions
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What do each of the 3 neuraminidase inhibitors do;
Oseltamivir
Zanamivir
Peramivir
Oseltamivir- orally active prodrug, hydrolyzed by the liver to its active form
AE: GI discomfort and headache
Zanamivir- inhaled or intranasal, or intravenous, avoid inhaled or intranasal with respiratory diseases or asthma
Peramivir- new neuraminidase inhibitor, intravenous only
AE: diarrhea & neutropenia
Oseltamivir and zanamivir are effective and safe for prophylaxis after exposure to and for treatment of influenza A and B
Slides 15-19
What is avian flu?
Uncoating inhibitors amantadine and rimantadine may have activity against some avian strains of influenza, but not against most of H5N1 subtype strains which caused avian flu outbreaks
Oseltamivir has been active against avian strains of influenza in animal studies (option for H5N1)
Zanamivir has been active in animal models, not studied in human infection with influenza
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What are viral uncoating inhibitors?
2 drugs
Amantadine
Rimantadine
Block the viral membrane matrix protein M2 (H+ ion channel)
Both orally administered for influenza A virus only
Both reported to be effective for prophylaxis and treatment of susceptible strains of influenza A
Resistance has increased substantially
Amantadine is effective in some Parkinson’s
Neither recommended anymore
Slides 20-21
What is ribavirin?
Synthetic guanosine analog, effective against RNA and DNA viruses
For treating severe RSV infections in infants and young children, and testing influenza
Effective in chronic hepatitis C infections
Inhibits GTP formation, viral mRNA capping, and thereby inhibits viral protein synthesis
Oral, intravenous, aerosol
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How do we treat hepatic viral infections?
Hepatitis B and C are most common for chronic hepatitis, cirrhosis, hepatocellular carcinoma
Chemotherapy is available for hepatitis B and C
Other drugs for HBV infection; adefovir, entecavir, telbivudine, tenofovir
What is interferon (IFN)?
Mode of action, adverse effects
Mode of action: induction of host cell enzymes that inhibit viral RNA translation, degradation of viral RNA, and stimulation of immune system
Peg-IFN-α-2a and peg-IFN-α-2b once weekly dosing, pegylatipn slows absorption, decreases clearance and provides higher serum concentrations
Administered intralesionally, subcutaneously, or IV
Adverse effects: flu like symptoms, bone marrow suppression, neurotoxicity, autoimmune disorders
What is lamivudine?
Mode of action, what it treats
Mode of action: inhibits both HBV DNA polymerase and HIV reverse transcriptase
Absorbed orally, well tolerated
For treatment of HBV and HIV infections
Slide 26
How do you treat HCV infection?
After HCV enters the hepatocyte, the viral genome is released from the nucleocapsid and then, an HCV polyprotein is translated
Polyprotein is cleaved by cellular and viral proteases to yield structural and non structural proteins
Several antivirals targeting NS3/NS4A protease, NS5B polymerase and NS5A protein involved in HCV replication and assembly are available
Slides 27-28
What are the 4 different kinds of drugs for HCV treatment?
NS3/NS4A protease inhibitors:
Paritaprevir, grazoprevir, voxilaprevir, glecaprevir
Previr = NS3/NS4
NS5B polymerase inhibitors:
Sofosbuvir, dasabuvir
Buvir = NS5B
NS5A replication complex inhibitors;
Ledipasvir, ombitasvir, elbasvirasvir, velpatasvir
Asvir = NS5A
Ribavirin: used for chronic HCV in combo with IFN or DAAs
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