LEC 9 - Antiviral Agents + Targets

Question 1

What is the conventional approach to control of viral diseases?

Answer 1

Vaccines

Question 2

What is the objective of antiviral drug therapy?

Answer 2

Eradicate virus

Minimally impact the host

Prevent further viral invasion

Question 3

What are the problems that people run into when developing anti-virals?

Answer 3

Need to penetrate host cells

Narrow therapeutic margin

Viral latency issues affect efficacy

Susceptibility testing is challenging/costly

Question 4

What is the common way to classify antiviral drugs?

Answer 4

Through their mechanism of action

Question 5

What are the five types of antivirals?

Answer 5

Immunomodulators

Ion channel blockers

Neuraminidase inhibitors

DNA/RNA synthesis inhibitors

Antiretroviral

Question 6

What is the basic way that ion channel blockers work?

Answer 6

Block uncoating

Question 7

What types of drugs are in the group of immunomodulators?

Answer 7

Interferons

Interleukins

Growth factors

Question 8

What is the most dominant immunomodulator?

Answer 8

Type 1 interferon

Question 9

What type of activity foes type 1 interferons have?

Answer 9

Antiviral activity

Immunomodulatory effects

Question 10

What is Feline interferon-omega used for?

Answer 10

Cats - FeLV + FIV

Dogs - Parvo virus

Question 11

What are the ion channel blockers?

Answer 11

Amantadines

(Amantadine + Rimantadine)

Question 12

What are the amatadines used for?

Answer 12

Influenza A viruses

Question 13

How does ion channel blockers work?

Answer 13

Block uncoating step of the life cycle

Insert into M2 protein channel - no H+ enters

No M1 protein dissociation

Keeps viral RNA within protein coat

Question 14

Whats the normal steps in viral uncoating?

Answer 14

Endosomal acidification

Active viral M2 channel protein - H+ enters virion

Viral M1 matrix protein dissociates = viral uncoating

Question 15

What causes resistance to ion channel blockers?

Answer 15

Mutations in M2 protein

Widespread, no longer recommended for use

Question 16

What drugs are in the neuraminidase inhibitor family?

Answer 16

Oseltamivir + Zanamivir

Question 17

What are the neuraminidase inhibitors used for?

Answer 17

Influenze A + B

Question 18

How do the neuraminidase inhibitors work?

Answer 18

Block the release of Influenze A + B from host cell membrane

Sialic acid analods

Bind to NA and prevent enzymatic acitivty

Inhibits viral release - can’t infect new cells

Question 19

What is the normal events that occur when Influenza A or B are released from the host cell?

Answer 19

replication occurs

Virus buds from host cell

remains bound to sialic acid on host cell membrane

Viral NA cleaves virus from salic acid

Virus released

Question 20

How does resistance to NA inhibitors occur?

Answer 20

Sporadic cases

Mutation in NA

Question 21

What infections has NA inhibitors been recommended for in dogs?

Answer 21

Canine parvo infection

Question 22

What are the types of antiviral agents that are considered DNA/RNA synthesis inhibitors?

Answer 22

Nuceloside synthesis inhibitor

Nucleoside analogs - DNA

Nucleoside analogs - RNA

Nucleoside + Non-nucleoside reverse transcriptase inhibitors

Question 23

How do nucleoside synthesis inhibitors work?

Answer 23

Directly inhibit DNA/RNA polymerase activity

Question 24

What are the nucleoside synthesis inhibitors?

Answer 24

Foscarnet

Question 25

What are the two types of nucleoside analogs for DNA syntesis?

Answer 25

Purine + Pyrimidine

Question 26

What are the purine analogs?

Answer 26

Acyclovir

Question 27

What are the pyrimidine analogs?

Answer 27

Cidofovir Idoxuridine Trifluridine

Question 28

What drugs are nucleoside analogs that interfere with viral RNA synthesis?

Answer 28

Ribavirin

Question 29

How does foscarnet work?

Answer 29

Direct inhibition of DNA polymerase Bind to pyrophosphate binding site Prevent cleavage of pryophosphate Halts DNA replication

Question 30

What viruses does foscarnet work for?

Answer 30

Wide range Herpesvirus -- and -- Retrovirus

Question 31

What can cause resistance to foscarnet?

Answer 31

Mutations in viral DNA polymerase

Question 32

How do nucleoside analogs work?

Answer 32

Inhibit viral DNA polyermase Chain termination activity Converted to triphosphate nucleotides in host cell

Question 33

What viruses are the target for nucleoside analog treatment?

Answer 33

Herpesvirus

Question 34

What is Acyvlovir a analog of?

Answer 34

dGTP

Question 35

How does Acyclovir work?

Answer 35

Inhibits replication ACV is converted to ACV-P by viral enzyme TK Competitive inhibitor of viral polymerase Higher affinity for DNA polymerase

Question 36

How is Acyclovir selective?

Answer 36

Uninfected cells will not change ACV into ACV-P

Question 37

How does resistance to Acyclovir occur?

Answer 37

Mutation in viral TK or DNA polymerase

Question 38

What are the prodrug derivatives of Acyclovir?

Answer 38

Valacylovir Famicilovir Valganciclovir

Question 39

What do all nucleoside analogs require?

Answer 39

Inital phosphorylation by virally-encoded enzymes

Question 40

What is ACV + PCV phosphorlylated by?

Answer 40

TK

Question 41

What is GCV phosphorylated by?

Answer 41

Viral Protein Kinase (PK)

Question 42

How does Vidarabine work?

Answer 42

Interferes with viral DNA polymerase activity

Question 43

How is vidarabine used in vet medicine?

Answer 43

FHV-1 ocular infections in cats Topical use ONLY

Question 44

What is cidofovir an analog of?

Answer 44

Deoxycytosine

Question 45

How does Cidofovir work?

Answer 45

Inhibitiion of polymerase activity Chain termination

Question 46

How do viruses become resistant to Cidofovir?

Answer 46

Mutations in DNA polymerase

Question 47

What does Cidofovir work against?

Answer 47

Herpes Adeno Poz Papilloma

Question 48

How can Cidofovir be used opthalmically?

Answer 48

Herpes eye infections in cats

Question 49

What are the two forms of pyrimidine analogs?

Answer 49

Idoxuridine Trifluridien

Question 50

What is the structure of Idoxuridine?

Answer 50

Iodine atom added to a uracil

Question 51

What is the structure of Trifluridine?

Answer 51

Contains -CF3 group added to Uracil

Question 52

How are Pyrimidine analogs used?

Answer 52

Feline herpes eye infectiosn

Question 53

What does Ribavirin resemble?

Answer 53

Purine analog Resembles RNA nucleotides

Question 54

How does Ribavirin work?

Answer 54

Immunomodulator - promote Th1 development Inhibits IMPDH enzyme - stops GTP synthesis Inhibits RNA-dependent RNA polymerase - RNA replication Promotes mutagenesis Interferes with mRNA capping

Question 55

How does ribavirin promote mutagenesis?

Answer 55

Resemble both A + G bases Incoporated into RNA

Question 56

What does ribavirin work against?

Answer 56

Both RNA + DNA viruses Works best against RNA respiratory viruses + Herpes

Question 57

How does resistance to antiretroviral agents develope?

Answer 57

Mutations at or near drugs binding site OR Mutations that change the conformation of target protien

Question 58

What is the antiretroviral used to treat FIV + FeLV?

Answer 58

AZT in combination with type I interferon

Question 59

How does Zifovudine work?

Answer 59

Selective inhibition of viral reverse transcriptase

Question 60

What are the non-nucleoside RT inhibitors?

Answer 60

Efavirenz Nevirapine Delavirdine

Question 61

How do the non-nucleoside RT inhibitors work?

Answer 61

Non-competively binding to reverse transcriptase + inhibiting its action

Question 62

What are the fusion/entry inhibitors?

Answer 62

maraviroc -- and -- Enfuvirtide

Question 63

How do the fusion/entry inhibitors work?

Answer 63

Interfere with receptor-mediated binding of virus to host -- or -- Prevent fusion of retroviral envelope with host cell membrane

Question 64

What are the integrase inhibitors?

Answer 64

Raltegravir -- and -- Elvitegravir

Question 65

How do integrase inhibitors work?

Answer 65

Inhibit integration of viral DNA into the host cell genome

Question 66

What are the protease inhibitors?

Answer 66

Saquinavir Ritonavir Indinavir

Question 67

How do the protease inhibitors function?

Answer 67

Binding to + inhibiting proteolytic activity of viral protease Prevent cleavage of polypeptide into functional proteins