antivirals

Question 1

Inhibitors of viral replication

Answer 1

– every step in viral replication is potentially a target

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

Question 2

Steps in virus replication
targeted by current
drugs and drugs in
development:

Answer 2

Question 3

Enfuvirtide

Answer 3

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

Question 4

Maraviroc

Answer 4

CCR5 binding inhibitor (HIV)

Question 5

Amantadine/ Rimantadine

Answer 5

• used to prevent influenza infections
• blocks penetration and uncoating of influenza A virus
Rimantadine = analog

Amantadine and rimantadine affect M2’s function as an ion channel
Following endocytosis, acidification of endosomes occurs
Then M2 can function as ion channel
Acidification within virion drives viral disassembly

Question 6

mAb Treatments for COVID-19

Answer 6

Monoclonal antibody (mAb) binds SARS-CoV-2 virions and “neutralizes” them, which
means it 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 7

Acyclovir 
targets what viruses? 
inhibits? 
rxn? 
effect on latency?

Answer 7

(nucleoside analog)
target herpesviruses
Inhibits DNA synthesis (DNA Poly)

Viral TK much more efficient than cellular TK in this reaction (so drug is specific to infected cells) However, acyclovir has no effect on latency

Question 8

Acyclovir/ CMV

Answer 8

is not effective against CMV

Question 9

Ganciclovir
effective against?
compared to acylcovir?
strucutre?

Answer 9

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

Gancicivir is nucleoside analog

Question 10

foscarnet
targets what viruses?
structure?

Answer 10

Directly inhibits herpesvirus and cytomegalovirus DNA polymerase (nephrotoxicity issues)

Foscarnet is a nonnucleoside inhibitor

Question 11

Remdesivir/ COVID

Answer 11

nucleoside analog

interferes with the action of viral RNA-dependent RNA polymerase causes RNA synthesis termination after a few nucleotides

Question 12

Hepatitis C virus treatments targets and their functions

Answer 12

Viral protease: cleaves viral proteins to their final mature sizes

Viral RNA-dependent RNA polymerase: viral genome replication and transcription

Question 13

Hepatitis C virus treatments
combos?
names?
others target?

Answer 13

Newer 2-drug combination therapies target specific HCV enzymes

Sofosbuvir: Inhibitor of RNA-dependent RNA polymerase
Ledipasvir: Inhibitor of RNA-dependent RNA polymerase

Other HCV treatments target viral protease

Question 14

Paxlovid

Answer 14

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

A peptidomimetic inhibitor

Question 15

Cidofovir
mainly used in?
what is it?

Answer 15

inhibits viral DNA polymerase, broad-spectrum anti-DNA virus drug

Use is mainly limited to cytomegalovirus retinitis in AIDS patients (toxicity limits dosage levels)

Cidofovir is a monophosphate nucleoside analog

Question 16

Anti-HIV drugs:

Answer 16

nucleoside analog reverse transcriptase inhibitors (NRTI)
nucleotide analog reverse transcriptase inhibitors (NtRTI)
nonnucleoside reverse transcriptase inhibitors (NNRTI)
Protease inhibitors
Integrase inhibitors

Question 17

nucleoside analog reverse transcriptase inhibitors (NRTI)

Answer 17

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 18

nucleotide analog reverse transcriptase inhibitors (NtRTI)

Answer 18

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

Question 19

nonnucleoside reverse transcriptase inhibitors (NNRTI)

Answer 19

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

Question 20

Protease inhibitors of HIV

Answer 20

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 21

HAART

Answer 21

highly active antiretroviral therapy, at least 3 drugs in combination
2 nucleoside inhibitors plus a NNRTI or a protease inhibitor

Question 22

Integrase inhibitors

Answer 22

Blocks integration of HIV dsDNA into host cell chromosomal DNA, interferes
with the strand transfer step

Question 23

Steps of HIV replication/infection that

are targeted by anti-viral therapies

Answer 23

entry
RT
integration
maturation

Question 24

Neuraminidase inhibitors

Answer 24

influenza virus neuraminidase (NA)= release of virus from envelope, cleaves sialic acid (NA has enzymatic activity)

Inhibitors prevent efficient spread of virus from cell to cell, tamiflu

Question 25

what can be used as a broader spectrum antiviral?

Answer 25

interferons

Question 26

Interferons

Answer 26

– natural products discovered in 1957
– Interferons assist the immune response
• inhibit viral replication within host cells
• activate natural killer cells and macrophages
• increase antigen presentation to lymphocytes

Question 27

Effects of interferon therapy

Answer 27

• Fatigue
• Fever
• Myalgias

Question 28

interferon therapy used to be for?

Answer 28

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

Question 29

Ribavirin
what is it?
what does it target?

Answer 29

• Purine nucleoside analog

• Inhibits many RNA viruses and some DNA viruses
– Influenza A and B
– Measles
– Respiratory Syncytial Virus