4.44 Flashcards
• Inhibitors of viral replication
2
– every step in viral replication is potentially a target
– targeting host cell functions is generally not feasible (toxicity)
Enfuvirtide - (4)
HIV fusion inhibitor
Binds to gp41 region that folds back onto itself
Prevents fusion of membranes
Very specific to HIV
Maraviroc – (1)
CCR5 binding inhibitor
amantadine virus entry
• used to prevent
influenza
infections
amantadine virus entry
• blocks
penetration
and uncoating of
influenza A virus
Rimantadine =
analog of amantadine
Amantadine and rimantadine affect
M2’s function as an ion channel
Amantadine and rimantadine affect M2’s function as an ion channel
(3)
Following endocytosis, acidification of endosomes occurs
Then M2 can function as ion channel
Acidification within virion drives viral disassembly
mAb active against
original version of SARS CoV-2
mAb active against original version of SARS CoV-2
received — from the FDA
Emergency Use Authorization
Monoclonal antibody (mAb)
binds SARS-CoV-2 virions and
“—” them, which
means it
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
Acyclovir - (3)
result of rational drug design (nucleoside analog)
target herpesviruses
Inhibits DNA synthesis
Viral genome replication
Acyclovir
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
Acyclovir is not effective against —
CMV
Ganciclovir is effective against
CMV
compared to acyclovir, although it is also
more toxic (cellular TK uses drug better too).
Gancicivir is — analog
nucleoside
foscarnet
Directly inhibits
herpesvirus and
cytomegalovirus
DNA polymerase
(nephrotoxicity issues)
Foscarnet is a
nonnucleoside inhibitor
Remdesivir is a nucleoside analog
interferes with the action of
viral RNA-dependent RNA polymerase
causes RNA synthesis termination after a few nucleotides
Viral protease:
cleaves
viral proteins to their
final mature sizes
Viral RNA-dependent RNA
polymerase:
viral genome
replication and transcription
Hepatitis C virus treatments:
Newer 2-drug combination therapies
target specific HCV enzymes
Other HCV treatments target
viral protease
sofosbuvir
Inhibitor of RNA-dependent
RNA polymerase
sofosbuvir
Inhibitor of
RNA-dependent
RNA polymerase
Ledipasvir
Inhibitor of
RNA-dependent
RNA polymerase
Paxlovid =
SARS-CoV-2
protease inhibitor: inhibits
production of mature
(cleaved) viral proteins
Paxlovid
A — inhibitor
peptidomimetic
Cidofovir is a relatively broad-spectrum
anti-DNA virus drug
Cidofovir
inhibits
viral DNA
polymerase
Cidofovir is a — analog
nucleoside
Use is mainly limited toc
cytomegalovirus retinitis in AIDS patients (toxicity limits dosage levels)
Anti-HIV drugs:
nucleoside analog reverse transcriptase inhibitors (NRTI)
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
Anti-HIV drugs:
nucleotide analog reverse transcriptase inhibitors (NtRTI)
Act like NRTI but do not need to be phosphorylated (already contain phosphate)
Anti-HIV drugs:
nonnucleoside reverse transcriptase inhibitors (NNRTI)
Bind sites on HIV RT enzyme that cause it to stop functioning, blocking reverse transcription
Anti-HIV drugs: Protease inhibitors
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
HAART =
highly active antiretroviral therapy
HAART = highly active antiretroviral therapy
at least – drugs in combination
– nucleoside inhibitors plus a NNRTI or a protease inhibitor
3
2
Anti-HIV drugs: Integrase inhibitors
Blocks integration of HIV dsDNA
into host cell chromosomal DNA
Integrase inhibitors
interferes with the
strand transfer step
Steps of HIV replication/infection that
are targeted by anti-viral therapies (4)
entry
reverse transcription
integration
maturation
Virus release
Neuraminidase inhibitors - influenza virus
neuraminidase (NA)
(3)
release of virus from envelope
cleaves sialic acid (NA has enzymatic activity)
Inhibitors prevent efficient spread of virus from cell to cell
Neuraminidase Inhibitors prevent
efficient spread of virus from cell to cell
• Interferons
2
– natural products discovered in 1957
– Interferons assist the immune response
• Interferons
– Interferons assist the immune response
- inhibit
- activate
- increase
viral replication within host cells
natural killer cells and macrophages
antigen presentation to lymphocytes
Effects of interferon therapy (3)
- Fatigue
- Fever
- Myalgias
Effects of interferon therapy
• Formerly (2)
main treatment
for hepatitis C Virus
(HCV) infection
used for HBV
Ribavirin (2)
• Purine nucleoside analog
• Inhibits many RNA viruses
and some DNA viruses
Ribavirin
• Inhibits many RNA viruses
and some DNA viruses
(3)
– Influenza A and B
– Measles
– Respiratory Syncytial Virus
