29 - viral life cycles and drug targets

Question 1

what are the seven steps in the virus life cycle

Answer 1

• Adsorption and penetration into cell
  
  • virus sticks to the cell through intermolecular forces then penetrates
• Capsid opens releasing contents
  
  • opens in the cell
• Synthesis of regulatory proteins
  
  • early proteins
• Synthesis of RNA or DNA
• Synthesis of structural proteins
  
  • late proteins
• Assembly of viral particles
  
  • assemble themselves
  • uses parts of the host cell
• Release from host cell

Question 2

describe the adsorption and penetration step of the viral life cycle

Answer 2

• Virus binds to host proteins on outside of host membrane
  
  • mediated by intermolecular forces between proteins on the virus and proteins on the host cell
  • Capsid binds directly and is passed inside before opening
  • Envelope fuses with host cell membrane releasing capsid inside the cell
• Genetic info is injected into the cell
  
  • Virus may also inject viral protein (enzyme or regulatory protein)
  • genetic information serves as a template for the manufacturing of certain early proteins that will take over the function of the cell
  • may get certain viral proteins that are already inside the capsid

Question 3

why are adsorption and penetration are poor drug targets

Answer 3

• Binding involves protein-protein interactions
  
  • Protein surface areas are very large
  • Difficult to inhibit protein-protein binding with small molecules

Question 4

in what virus was there limited success in terms of adsorption and penetration

Answer 4

• Limited success in HIV
  
  • Fuzeon – peptide with 36 amino acids
    
    • big molecule
  • Maraviroc – small molecule
    
    • true small molecule
    • HIV virus has a small protein on the outside of it that functions like a little drill. when the protein on the outside of the HIV binds to the receptor on the human cell, it literally drills itself through the membrane of the host. drilling action happens because the HIV viral protein changes shape when it comes into contact with human protein. maraviroc has the ability to attach to the little drill protein → prevents it from unwinding

Question 5

describe the process of release of viral nucleic acid

Answer 5

• Capsid opens releasing genetic information into the cell
  
  • Difficult to target (protein interactions, pH changes)
• Two successful drugs
  
  • Influenza
    
    • amantadine and rimantidine
  • Block an ion channel
    
    • found on the capsid of the influenza
    • very specialized structure (unique 3D shape)

Question 6

describe the process of the synthesis of regulatory proteins

Answer 6

• Viral proteins are made
• “take over” normal cell systems
  
  • Nucleic acid replication
    
    • viral nucleic acid replication
  • Expression of viral protein
    
    • viral nucleic acids are used to manufacture viral proteins
  • Suppression of host cell defenses (apoptosis)
    
    • certain viruses have the ability to prevent apoptosis
  • Binding to host proteins
• No drugs currently exist for this phase

Question 7

describe the process of synthesis of RNA and DNA

Answer 7

• Viral genome is replicated using host enzymes
  
  • can be RNA or DNA
  • enzymes called polymerases
• Some viruses have their own enzymes for this (drug targets)
  
  • a lot of viruses just use human polymerases
• Most anti-viral drugs target this phase
  
  • uses an enzyme that many viruses carry
  • Require unique viral enzyme
    
    • cant target a virus that uses host enzymes
  • Prevent viral nucleic acid synthesis

Question 8

describe the process of synthesis of structural proteins

Answer 8

• Utilize the host Ribosome
  
  • Poor drug target
  • ribosome make all the proteins in the cell
• Some viruses utilize specific enzymes for protein maturation
  
  • many viruses express their proteins as a long linear chain that is composed of all the sub-proteins linked together. carry their own special enzyme called protease which will cut the chain in parts and release the individual proteins
  • Protease drugs
    
    • HIV
    • Hepatitus C
    • covid also has protease in it

Question 9

describe the process of assembly and release

Answer 9

• Capsid proteins self-assemble
  
  • tuck Nucleic acid inside
  • Viral proteins outside
• Release may destroy cell
  
  • Lytic virus herpes, influenza
    
    • herpes forms a lytic infection in skin cells
• Cell may remain intact
  
  • becomes a factory for the virus
  • Papilloma, herpes
    
    • herpes stays in tact in your nerve cells, this is how you carry it for your whole life
• Only a few drug targets (HIV, influenza)

Question 10

what do antiviral drugs require

Answer 10

• enzyme targets
• Enzyme should be structurally unrelated to host enzymes
  
  • want it as different in its 3D shape as possible to have distinct binding pockets
  • Provides selectivity