Antivirals Flashcards
What happens in attachment as part of viral replication?
Virus attaches to a specific receptor site on the host cell membrane through attachment proteins in the capsid or glycoproteins embedded in the viral envelope
How do viruses enter the host cell?
Endocytosis
What happens in uncoating?
Viral capsid is degraded
Viral nucleic acid is released which becomes available for replication and transcription
What happens in replication?
DNA viruses use host cell proteins and enzymes to make additional DNA that can be transcribed into mRNA and translated
RNA viruses use RNA core as a template for synthesis of genomic RNA and mRNA
How do retroviruses replicate?
Their RNA genome must be reverse transcribed into DNA
This incorporated into the host cell genome
What happens in assembly?
Viral mRNA directs the host cell to synthesise viral enzymes and capsid proteins and to assemble new virions
What happens in release?
New virions are released either when the host cell dies or by budding through the membrane without killing the cell
What are the features of the influenza virus?
- enveloped/not enveloped?
- type of nucleic acid?
- number of strands?
Enveloped
RNA
Single stranded
Which influenza virus shows antigenic shift and drift and can have multiple host species?
Influenza A
Does influenza B have antigenic shift and drift?
Yes - changes each year
What are the two antigens that influenza viruses have?
Neuraminidase
Haemaggluttin
How does the influenza virus gain entry into cells?
Attaches to a neuraminic or sialic acid residue on a membrane glycoprotein
There is ATP-driven proton entry into the endosome to allow fusion of the viral membrane with the internal endosomal membrane
Entry of protons into the virus itself via M2
Low pH inside the virus causes breakdown of the viral coat of the nucleocapsid
RNA can escape into the host cell cytoplasm
Where is the M2 ion channel found?
In the viral envelope of influenza A
What activates the M2 ion channel?
Low pH seen during receptor-mediated endocytosis
Function of the M2 ion channel?
Brings protons into the virion core leading to acidification, causing uncoating so that the nucleus can start viral replication
Which drugs can inhibit the M2 ion channel?
Amantadine and rimantadine
What is the effect of Amantadine and rimantadine?
Block the M2 ion channel, preventing uncoating of the virus
How can resistance to Amantadine and rimantadine occur?
Mutations to the M2 channel
Side effects of amantadine and rimantadine?
GI
- nausea
- vomiting
- diarrhoea
- constipation
- loss of appetite
CNS
- dizziness
- nervousness
- insomnia
- confusion
- hallucination
Hypotension
Which of the M2 inhibitors have a higher ADR risk?
Amantadine
What does neuraminidase do in influenza viruses?
Allows release of the new virion from the host cell
- virus egresses from the host cell while re-attaching to the sialic acid membrane glycoprotein residues on the cell membrane
- needs to be cleaved from the residues which is done by neuraminidase
Why is neuraminidase a good target for antivirals?
Its active site is conserved across subtypes
What are neuraminidase inhibitors and what allows them to bind over sialic acid?
Sialic analogues
Have high binding affinities and potency so bind more strongly than competing endogenous sialic acid
Which types of influenza can neuraminidase inhibitors be used to treat?
Influenza A and B
Name the two neuraminidase inhibitors
Zanamavir
Oseltamivir (Tamiflu)
Bioavailability of zanamavir and Tamiflu?
Zanamavir has low bioavailability as destroyed by gut
Tamiflu has a high bioavailability (80%) - a prodrug
How are zanamavir and Tamiflu administered?
Zanamavir is a dry powder aerosol
Tamiflu given orally
ADRs of neuraminidase inhibitors?
GI disturbance
Headache
Nose bleeds
Respiratory depression
Bronchospasm
What is resistance like for neuraminidase inhibitors?
Low - evolutionarily conservative
Resistance in H5N1 (bird flu)
What are the six steps in viral replication?
Attachment Entry Uncoating Replication Assembly Release
