Lecture 9: Antiviral agents and targets

Question 1

What is the objective of antiviral therapy

Answer 1

to inhibit viral replication while eliciting minimal toxicity to the host

Question 2

t or f: antivirals have to be administered early to be efficacious for acute infections

Answer 2

true

Question 3

what is the most common antiviral used and for treatment of what

Answer 3

nucleoside analogs for tx for herpesviruses and retroviruses

Question 4

what are the 4 classifications of antiviral drugs

Answer 4

1. Immune modulators
   2, anti-influenza antivirals
2. DNA/RNA synthesis inhibitors
3. Protease, integrase, and entry inhibitors

Question 5

what do DNA/RNA synthesis inhibitors target (what viruses)

Answer 5

herpesviruses and retroviruses

Question 6

what do proteases, integrases, and entry inhibitors target (what viruses)

Answer 6

retroviruses

Question 7

immunomodulators are substances that either ___ or __ the immune system

Answer 7

stimulate or suppress

Question 8

What type of antiviral is type I interferon

Answer 8

immunomodulator

Question 9

how does type I interferon work

Answer 9

acts by triggering RNAses to degrade viral RNA and protein kinases that inhibit host and viral protein synthesis

Question 10

what drug has been shown to be effective against FIV and FeLV

Answer 10

Feline interferon-omgea- type I interferon

Question 11

what are the 3 broad classes of anti-influenza anti-viral agents

Answer 11

1. Adamantane derivatives
2. Neuraminidase inhibitors
3. Polymerase inhibitors

Question 12

what anti-vital has been used against influenza A viruses

Answer 12

adamantanes

Question 13

how do adamantanes work (amantadine, rimantadine). Understand how normal process works and how adamantanes block

Answer 13

block the uncoating step of life cycle,

Normal uncoating: endosomal acidic action, active viral M2 channel protein allows H+ ions to enter virion, viral M1 matrix protein dissociates results in viral uncoating- adamantanes block the uncoating

Question 14

hemagglutinin binds to __which is used to __

Answer 14

sialic acid, adhere to host cells

Question 15

viral Neuraminidase cleaves __, releasing __

Answer 15

sialic acid, releasing viruses from membranes

Question 16

what type of drug is oseltamivir

Answer 16

Neuraminidase inhibitors

Question 17

what are Neuraminidases used against

Answer 17

influenza A and B viruses

Question 18

how do neuramindases inhibitors work/sialic acid analogs

Answer 18

binding neuramindase and preventing enzymatic activity- inhibits viral release from membrane and prevents viruses from infecting new host cell

Question 19

what is the mechanism of resistance to oseltamivir

Answer 19

mutations in neuroamindase that arise randomly during RdRp mediated replication, followed by selecting

Question 20

what drug has been shown to improve clinical signs against parvovirus

Answer 20

oseltamivir

Question 21

how does oseltamivir work for parvovirus since it does not contain Neuraminidase

Answer 21

acts on bacterial Neuraminidase from enteric bacteria

Question 22

how do purine analogs: acyclovir and derivatives and pyrimidine analogs: cidofovir work

Answer 22

interfere with viral DNA synthesis

Question 23

how do purine analogs: remdesivir work

Answer 23

Interfere with viral RNA synthesis

Question 24

how do pyrimidine analogs: zidovudine work

Answer 24

interfere with retroviral DNA synthesis

Question 25

how do non-nucleoside reverse transcriptase inhibitors work

Answer 25

interfere with retroviral DNA synthesis

Question 26

how do nucleoside analogs work

Answer 26

inhibit viral DNA polymerase and have chain termination activity

Question 27

nucleoside analogs are converted to __ in host cell

Answer 27

triphosphate nucleotides (active form_

Question 28

what are nucleoside analogs primarily effective against

Answer 28

herpesviruses

Question 29

acyclovir is an analog of __ and what is it used to tx

Answer 29

analog of deoxyguanosine that selectively inhibits replication of herpesvirus, primarily alpha-herpesviruses

Question 30

how does acyclovir become its active form

Answer 30

converted to ACV-P by the viral enzyme thymidine kinase

Question 31

acyclovir is a competitive inhibitor of __

Answer 31

viral DNA polymerase

Question 32

ACV-triphosphate has much higher affinity for __

Answer 32

viral DNA polymerase

Question 33

incorporation of ACV-triphosphate results in __

Answer 33

chain termination

Question 34

How does acyclovir achieve selective toxicity

Answer 34

uninfected cells do not convert ACV to ACV-P

Question 35

how does resistance occur with acyclovir

Answer 35

mutations to viral thymidine kinase or DNA polymerase

Question 36

what are the derivatives of acyclovir (prodrugs)

Answer 36

1. Valacyclovir- converted to ACV 2. Famciclovir- converted to penciclovir

Question 37

what are valacyclovir and famciclovir used against

Answer 37

alphaherpesvirus

Question 38

all acyclovir derivatives require __ by virally encoded enzymes. How does that occur

Answer 38

phosphorylation, via viral thymidine kinase

Question 39

vidarabine is an analog of __

Answer 39

adenosine

Question 40

what is the mechanism of action for vidarabine

Answer 40

interferes with viral DNA polymerase activity

Question 41

what is vidarabine used for

Answer 41

FHV-1 ocular infections in cats

Question 42

Remdesivir is a __ analog

Answer 42

adenosine

Question 43

how does remdesivir work

Answer 43

inhibits viral RNA-dependent RNA polymerase

Question 44

what is remdesivir used to tx

Answer 44

FIP caused by feline coronavirus

Question 45

cidofovir is an analog of __

Answer 45

nucleoside deoxycytosine

Question 46

how does cidofovir work

Answer 46

inhibition or polymerase activity and chain termination

Question 47

What is the mechanism of resistance against cidofovir

Answer 47

mutations in DNA polymerase

Question 48

what does cidofovir tx

Answer 48

1. Herpesviruses- eye infections in cats 2. Adenovirus 3. Pox viruses 4. Papilloma viruses

Question 49

what does zidovudine tx

Answer 49

cats with severe dental inflammation or neurological disease

Question 50

Zidovudine is an analog of __, containing __ of sugar

Answer 50

thymidine, azide

Question 51

zidovudine is a __ inhibitor

Answer 51

nucleoside reverse transcriptase inhibitor

Question 52

how does zidovudine work

Answer 52

inhibition of viral reverse transcriptase activity, synthesizes DNA from DNA

Question 53

what is zidovudine used to tx

Answer 53

FeLV in cats

Question 54

How do entry inhibitors work

Answer 54

prevent viral attachment/entry into the host cells

Question 55

how do integrase inhibitors (raltegravir) work

Answer 55

prevent incorporation of the pro viral DNA into the genome of host cell

Question 56

how do protease inhibitors work

Answer 56

prevent cleavage of pro-protein into functional polypeptides