pharmacology

• what components do viruses not have?

  cell wall and membrane

  organelles
• how many strands do DNA viruses have?

  they can be both single and double stranded
• where do dna viruses replicate?

  host cell nucleus
• how do viruses enter a host cell?

  they express polypeptide binding sites on their envelope or capsid which bind to host cell surface receptors.

  note- each virus type attaches to a different cell
• describe the viral life cycle?


  attachment- specific binding to host cell surface receptors

  entry- membrane fusion, then endocytosis

  uncoating/eclipse phase- viral capsid (the layer below the envelope) is removed releasing nucleic acids

  replication- viral nucleic acids and components replicated using host cell machinery

  assembly - viral components assembled into complete viral particles

  Release - lysis or budding of viral particles , for infection of new host cell
• what types of treatment are there for viral infections?

  no treatment- relying on immune systems of healthy individuals

  therapeutic- antiviral drugs after signs of infection (clinical symptoms occur late, when the virus has replicated)

  prophylactically - for at risk groups (look this over)

  prevention- immunisation
• what part of the viral life cycle do anti-viral agents target?

  attachment to host cell

  uncoating

  synthesis of viral mRNA

  Translation of mRNA

  replication of viral RNA or DNA

  (above 3 fall under the replication process)

  maturation/assembly of new viral protein

  budding,release
• what are the main 9 infectious diseases that antiviral therapeutics target?

  look below

  
• what 2 drugs target the uncoating process of the viral life cycle? Explain how.


  Amantadine and Rimantadine.

  block ion channel proteins which play a role in disintegrating the viral capsid
• what viral diseases are amantadine and rimantadine active against?

  Influenza A. They are used PROHYLACTICALLY
• What is the main target for antiviral drugs that target the viral replication process of the viral life cycle?

  specificity in virus polymerase.

  NOTE- when you have a specific viral target that means there is a low chance of toxicity to the host
• what part of the viral process do the majority of the antiviral drugs target?


  Replication
• what are synthetic nucleoside analogues and what are they used for ?

  pro-drugs

  once taken up they are phosphorylated to active form (triphosphate)

  triphosphate inhibits:

  • viral DNA/RNA polymerase
  • Reverse transcriptase

  or triphosphate is incorporated into growing viral DNA leading to abnormal proteins or breakage
• give 2 examples of a nucleoside analogue.

  Acyclovir and Ganciclovir
• what is acyclovir used to treat and how does it work?

  herpes virus-HSV and vzv.

  inhibits viral DNA polymerase

  competitively inhibits viral DNA polymerase and gets incorporated into DNA resulting in chain termination.

  It competitively inhibits VIRAL DNA POLYMERASE because it is an analogue to deoxyguanosine triphosphate (dGTP)

  note - it has a higher affinity for viral DNA polymerase than for cellular DNA polymerase
• what is ganciclovir used to treat and why?

  cytomegalovirus. Ganciclovir is phosphorylated by a viral kinase encoded by a CMV gene. Hence why ganciclovir is used to treat cytomegalovirus and not acyclovir.
• for what patients i ganciclovir particularly dangerous?

  pregnant women ( can get passed to the baby) and those with weakened immune systems.

  however, usually harmless for normal people
• what are interferons?

  host cytokines produced by the immune system in response to the challenge.
• how do interferons work?

  they induce ( bring about) intracellular signals that result in the inhibition of:

  viral penetration

  viral translation, transcription, protein processing

  viral release
• what do antiviral interferons do?

  they have been developed to promote the production and release of interferons.
• what are neuraminidase inhibitors and how do they work?

  they are a drug specific to influenza.

  influenza contains an enzyme called neuraminidase that allows for the release of virions and their spread from cell to cell.

  neuraminidase inhibitors block this enzyme and process.
• what are some examples of neuraminidase inhibitors?

  Oseltamivir, Zanamivir.

  Note- oseltamivir is reported to be 90% effective as a prophylactic agent against influenza.
• SARS-Cov-2: severe acute respiratory syndrome coronavirus 2.

  is an RNA virus - single-stranded
• what host cell surface receptors does SARS-Covid-2 attach to?

  angiotensin-converting enzyme 2 (ACE2) receptor
• what are some examples of antiviral drugs for sars-cov-2?

  remdesivir, molnupiravir, paxlovid
• what are some examples of Anti-sars-cov-2 monoclonal antibodies?

  Bamlanivimab, Casirivimab, and Imdevimab.
• what are some examples of anti-inflammatory drugs for sars-cov-2?

  IMMUNOMODULATORS are available under FDA issued emergency use
• what are retrovirals?

  RNA viruses which synthesise DNA from an RNA template.

  
• what type of virus is human immunodeficiency virus (HIV)?

  RNA retrovirus
• how does HIV interact with the hosts immune system?

  binds to T-helper cells (CD4+ T lymphocytes) and reduces their count.
• what are the 2 types of HIV and what do they lead to?

  HIV-1= can lead to the development AIDS

  HIV-2= causes immune suppression but is less virulent
• what is the structure of HIV like?

  below

  
• describe the HIV lifecycle:

  1. fusion of HIV to the host cell surface,
  2. HIV RNA, integrase, reverse transcriptase and other proteins enter host cell
  3. viral DNA is formed by reverse transcriptase
  4. viral DNA is integrated into host cell by integrase
  5. New viral RNA is used to make viral proteins
  6. new viral RNA and viral proteins move to the cell surface, a new immature HIV forms
  7. virus is released. viral protease cleaves new polyproteins to create mature infectious virus.
• what parts of the retroviral life cycle do antiretrovirals target?

  fusion (by fusion inhibitors)

  reverse transcriptase ( by reverse transcriptase inhibitors)

  viral DNA integration- (by integrase strand transfer inhibitors)

  viral release by protease inhibitors
• what are the two reverse transcriptase inhibitors called?

  non-nucleoside reverse transcriptase inhibitors (NNRTIs)

  nucleoside reverse transcriptase inhibitors (NRTIs)
• how does nucleoside reverse transcriptase target retroviral replication?

  Process very similar to synthetic nucleoside analogues for viruses that aren't retroviral.

  They enter the cell as a pro-drug and are phosphorylated to their active form

  competitively inhibit nucleotides from binding to reverse transcriptase and are incorporated into growing DNA.

  this terminates the DNA
• what is the adverse effect of using Zidovudine the Nucleoside Reverse Transcriptase Inhibitor?

  Bone marrow suppression.
• How do non nucleoside reverse transcriptase work?

  they-competitively bind to reverse transcriptase at a different site to NRTIs (allosteric site) and inactivate it.
• does non- nucleotide reverse transcriptase require phosphorylation to be active?

  No.
• is non-nucleoside reverse transcriptase inhibitor (NNRTI) incorporated into DNA?

  No.