4.44

Question 1

• Inhibitors of viral replication

2

Answer 1

– every step in viral replication is potentially a target

– targeting host cell functions is generally not feasible (toxicity)

Question 2

Enfuvirtide - (4)

Answer 2

HIV fusion inhibitor
Binds to gp41 region that folds back onto itself
Prevents fusion of membranes
Very specific to HIV

Question 3

Maraviroc – (1)

Answer 3

CCR5 binding inhibitor

Question 4

amantadine virus entry

• used to prevent

Answer 4

influenza

infections

Question 5

amantadine virus entry

• blocks

Answer 5

penetration
and uncoating of
influenza A virus

Question 6

Rimantadine =

Answer 6

analog of amantadine

Question 7

Amantadine and rimantadine affect

Answer 7

M2’s function as an ion channel

Question 8

Amantadine and rimantadine affect M2’s function as an ion channel
(3)

Answer 8

Following endocytosis, acidification of endosomes occurs
Then M2 can function as ion channel
Acidification within virion drives viral disassembly

Question 9

mAb active against

Answer 9

original version of SARS CoV-2

Question 10

mAb active against original version of SARS CoV-2

received — from the FDA

Answer 10

Emergency Use Authorization

Question 11

Monoclonal antibody (mAb)
binds SARS-CoV-2 virions and
“—” them, which
means it

Answer 11

neutralizes

blocks the virus
from interacting with ACE2
receptors and entering cells
mAb was isolated from a recovered
COVID-19 patient = a neutralizing
IgG1 mAb directed against the
SARS-CoV-2 spike (S) protein

Question 12

Acyclovir - (3)

Answer 12

result of rational drug design (nucleoside analog)
target herpesviruses
Inhibits DNA synthesis

Question 13

Viral genome replication
Acyclovir
Viral TK much more efficient than

Answer 13

cellular TK in this

reaction (so drug is specific to infected cells)

Question 14

However, acyclovir has no effect on —

Answer 14

latency

Question 15

Acyclovir is not effective against —

Answer 15

CMV

Question 16

Ganciclovir is effective against

Answer 16

CMV
compared to acyclovir, although it is also
more toxic (cellular TK uses drug better too).

Question 17

Gancicivir is — analog

Answer 17

nucleoside

Question 18

foscarnet

Directly inhibits

Answer 18

herpesvirus and
cytomegalovirus
DNA polymerase
(nephrotoxicity issues)

Question 19

Foscarnet is a

Answer 19

nonnucleoside inhibitor

Question 20

Remdesivir is a nucleoside analog

interferes with the action of

Answer 20

viral RNA-dependent RNA polymerase

causes RNA synthesis termination after a few nucleotides

Question 21

Viral protease:

Answer 21

cleaves
viral proteins to their
final mature sizes

Question 22

Viral RNA-dependent RNA

polymerase:

Answer 22

viral genome

replication and transcription

Question 23

Hepatitis C virus treatments:

Answer 23

Newer 2-drug combination therapies

target specific HCV enzymes

Question 24

Other HCV treatments target

Answer 24

viral protease

Question 25

sofosbuvir

Answer 25

Inhibitor of RNA-dependent | RNA polymerase

Question 26

sofosbuvir | Inhibitor of

Answer 26

RNA-dependent | RNA polymerase

Question 27

Ledipasvir | Inhibitor of

Answer 27

RNA-dependent | RNA polymerase

Question 28

Paxlovid =

Answer 28

SARS-CoV-2 protease inhibitor: inhibits production of mature (cleaved) viral proteins

Question 29

Paxlovid | A --- inhibitor

Answer 29

peptidomimetic

Question 30

Cidofovir is a relatively broad-spectrum

Answer 30

anti-DNA virus drug

Question 31

Cidofovir | inhibits

Answer 31

viral DNA | polymerase

Question 32

Cidofovir is a --- analog

Answer 32

nucleoside

Question 33

Use is mainly limited toc

Answer 33

``` cytomegalovirus retinitis in AIDS patients (toxicity limits dosage levels) ```

Question 34

Anti-HIV drugs: | nucleoside analog reverse transcriptase inhibitors (NRTI)

Answer 34

Need to be phosphorylated by cellular enzymes before being used by HIV reverse transcriptase (RT) (like acyclovir). HIV RT uses these analogs and since they lack a 3’ –OH, DNA synthesis (reverse transcription) stops

Question 35

Anti-HIV drugs: | nucleotide analog reverse transcriptase inhibitors (NtRTI)

Answer 35

Act like NRTI but do not need to be phosphorylated (already contain phosphate)

Question 36

Anti-HIV drugs: | nonnucleoside reverse transcriptase inhibitors (NNRTI)

Answer 36

Bind sites on HIV RT enzyme that cause it to stop functioning, blocking reverse transcription

Question 37

Anti-HIV drugs: Protease inhibitors

Answer 37

HIV protease cleaves the initial HIV proteins to their final mature sizes Protease inhibitors attempt to mimic an HIV protease cut site, competitively inhibiting HIV protease Peptidomimetic inhibitors

Question 38

HAART =

Answer 38

highly active antiretroviral therapy

Question 39

HAART = highly active antiretroviral therapy at least -- drugs in combination -- nucleoside inhibitors plus a NNRTI or a protease inhibitor

Answer 39

3 | 2

Question 40

Anti-HIV drugs: Integrase inhibitors

Answer 40

Blocks integration of HIV dsDNA | into host cell chromosomal DNA

Question 41

Integrase inhibitors | interferes with the

Answer 41

strand transfer step

Question 42

Steps of HIV replication/infection that | are targeted by anti-viral therapies (4)

Answer 42

entry reverse transcription integration maturation

Question 43

Virus release Neuraminidase inhibitors - influenza virus neuraminidase (NA) (3)

Answer 43

release of virus from envelope cleaves sialic acid (NA has enzymatic activity) Inhibitors prevent efficient spread of virus from cell to cell

Question 44

Neuraminidase Inhibitors prevent

Answer 44

efficient spread of virus from cell to cell

Question 45

• Interferons | 2

Answer 45

– natural products discovered in 1957 | – Interferons assist the immune response

Question 46

• Interferons – Interferons assist the immune response * inhibit * activate * increase

Answer 46

viral replication within host cells natural killer cells and macrophages antigen presentation to lymphocytes

Question 47

Effects of interferon therapy (3)

Answer 47

* Fatigue * Fever * Myalgias

Question 48

Effects of interferon therapy | • Formerly (2)

Answer 48

main treatment for hepatitis C Virus (HCV) infection used for HBV

Question 49

Ribavirin (2)

Answer 49

• Purine nucleoside analog • Inhibits many RNA viruses and some DNA viruses

Question 50

Ribavirin • Inhibits many RNA viruses and some DNA viruses (3)

Answer 50

– Influenza A and B – Measles – Respiratory Syncytial Virus