Antiviral Treatment Strategies- Exam IV Flashcards
Antiviral treatment strategies/targets include:
- inhibitors of viral replication
- virus entry
- viral genome replication
- viral release
Every step in ___ is a potential target for antiviral treatment
viral replication
Targeting ___ is generally not a feasible antiviral treatment strategy:
host cell functions
Why is targeting host cell function generally not feasible?
due to toxicity
What type of antiviral drugs act on the penetration step?
Enfuvirtide and fusion inhibitors
What type of antiviral drugs act after penetration and before uncoating?
Rimantadine & Amantadine
What type of antiviral drugs act on the genome replication step?
- Acyclovir
- Ganciclovir
- Foscarnet
- HIV reverse transcriptase inhibitors
What type of antiviral drugs act after genome replication but before RNA synthesis?
- Ribavirin and Interferon
What type of antiviral drugs after RNA synthesis and before protein synthesis?
Interferon
What type of antiviral drugs act after assembly but before release?
neuraminidase inhibitors
HIV fusion inhibitor that binds to gp41 region that folds back onto itself and prevent fusion of membranes (very specific to HIV)
Enfuvirtide
Enfuvirtide is a ___ fusion inhibitor:
HIV fusion inhibitor
Enfuvirtide binds to ___ region that folds back onto itself and prevents ____
gp41; fusion of membranes
CCR5 binding inhibitor =
maraviroc
What step do both enfuvirtide and maraviroc work at?
virus entry
This step in viral infection is used to prevent influenza infections and blocks penetration and uncoating of influenza A virus:
virus entry
The drug used to prevent influenza entry and blocks penetration and uncoating of influenza A virus (basically blocks virus entry):
amantadine
Analog of Amantadine:
Rimantadine
Amantadine and Rimantadine affect:
M2’s function as an ion channel
How does manta dine and rimantadine affect M2’s function as an ion channel?
following endocytosis, acidification of endosomes occur, and then M2 can function as ion channel and the acidification within virion drives the viral disassembly
Following endocytosis acidification of ____ occurs, then ___ can function as an ion channel
endosomes; M2
Acidification within virions drives:
viral disassembly
Monoclonal antibodies (mAb’s) against SARS Coverage-2 are:
viral entry inhibitors
What is one treatment option for Covid-19?
Monoclonal antibodies
The monoclonal antibodies used to treat covid, bind ___ & ____
SARS-Cov-2 virions & neutralize them
Monoclonal antibodies bind SARS-Cov-2 virions and neutralize them meaning:
they block the virus from interacting with ACE2 receptors and entering cells
The first monoclonal Ab for treating Covid-19 was derived from:
a patient that had recovered from the disease
When deriving the first monoclonal antibodies, the patient that had recovered from the disease had serum that contained:
A neutralizing IgG1 antibody directed against SARS-CoV-2 spike protein
Result of rational drug design (nucleoside analog) that targets herpresviruses by inhibiting DNA synthesis:
Acylcovir
Acyclovir inhibits:
DNA synthesis
Why is acyclovir specific to infected cells?
Viral thymidine kinase (TK) is much more efficient than cellular TK
Describe acyclovirs effects on latency:
No effect on latency
What are two drugs structurally similar to acyclovir?
- Deoxyguanosine
- Ganciclovir
How does Acyclovir progress to acyclovir monophosphate?
acted on by viral TK and ATP
How does acyclovir monophosphate progress to acyclovir triphosphate?
acted on by cellular kinases and ATP
Acyclovir is not effective against what herpesvirus?
CMV
Drug that is effective against CMV compared to acyclovir, although it is more toxic:
Ganciclovir
Why is Ganciclovir more toxic compared to acyclovir?
Cellular TK uses drug better too
What is the nucleoside analog to Ganciclovir?
Gancicivir
Drug that DIRECTLY inhibits herpesvirus and cytomegalovirus DAN polymerase:
Foscarnet
What issues are seen with Foscarnet use?
Nephrotoxicity issues
Foscarnet is considered a ___ inhibitor
non-nucleoside
____ is a nucleoside analog that interferes with the action of viral RNA-dependent RNA polymerase
Remdesivir
How does Remdesivir work?
Interferes with the action of viral RNA-dependent RNA polymerase and causes RNA synthesis termination after a few nucleotides
What virus does Remdesivir treat?
Covid-19
In Hepatitis C, what is responsible for cleaving the viral proteins to their final mature sizes?
Viral Protease
In Hep C virus, what is responsible for viral genome replication and transcription?
Viral RNA-dependent RNA polymerase
Discuss the treatment for Hep C virus:
Newer 2-drug combination therapies target specific HCV enzymes
For Hep C, the new 2-drug combination therapies target specific:
HCV enzymes
A HepC treatment that functions as an inhibitor of RNA-dependent RNA polymerase:
Sofosbuvir & Ledipasvir
In addition to targeting specific HCV enzymes & inhibiting RNA-dependent RNA polymerase, other HCV treatments target:
viral protease
A SARS-CoV-2 protease inhibitor that inhibits the production of mature (cleaved) viral proteins
Paxlovid
Paxlovid inhibits:
production of mature (cleaved) viral proteins
Paxlovid is considered a protease inhibitor, but more specifically a:
peptidomimetic inhibitor
If we talking about a peptidomimetic inhibitor we are discussing:
paxlovid
___ is a very broad-spectrum anti-DNA virus drug:
Cidofovir
Cidofovir inhibits:
viral DNA polymerase
This drug is a nucleoside analog, use is mainly limited to cytomegalovirus retinitis in AIDS patients (toxicity limits dosage levels)
Cidofovir
List the categories of anti-HIV drugs:
- nucleoside analog reverse transcriptase inhibitors (NRTI)
- nucleotide analog reverse transcriptase inhibitors (NtRTI)
- Nonnucleoside reverse transcriptase inhibitors (NNRTI)
Anti-HIV drug that needs to be phosphorylated by cellular enzymes before being used by HIV reverse transcriptase (RT) (like acyclovir):
NRTI
HIV RT uses these analogs and since they lack a 3’ -OH , DNA synthesis (reverse transcription) stops:
nucleoside analog reverse transcriptase inhibitors (NRTI)
Act like NRTIs but do not need to be phosphorylated (because they already contain a phosphate)
nucleotide analog reverse transcriptase inhibitors (NtRTI)
Binds site on HIV RT enzyme that cause it to stop functioning, blocking reverse transcription:
NNRTI- non nucleoside reverse transcriptase inhibitors
HIV protease cleaves the initial HIV proteins to their final mature sizes, so these drugs attempt to mimic an HIV protease cut site, competitively inhibiting HIV protease:
protease inhibitor (anti-HIV drug)
Protease inhibitors used to treat HIV may also be referred to as:
peptidomimetic inhibitors
HAART:
Highly active antiretroviral therapy
at least 3 drugs in combination including 2 nucleoside inhibitors plus a NNRTI or protease inhibitor:
HAART
Anti-HIV drug that blocks integration of HIV dsDNA into host cell chromosomal DNA
Integrase inhibitor
What step do integrate inhibitors interfere with?
with the strand transfer step
Steps in HIV replication/infection that are targeted by antiviral therapies:
- entry
- reverse transcription
- integration
- maturation
Neuraminidase inhibitors are used against what virus and target what step?
influenza virus, release of virus from envelope
How do neuraminidase inhibitors function?
Cleaves sialic acid
What allows neuraminidase inhibitors to cleave sialic acid?
neuraminidase has enzymatic activity
Neuraminidase inhibitors preven efficient:
spread of virus from cell to cell
Give an example of an neuraminidase inhibitor used against influenza virus:
tamiflu
A broader spectrum antiviral:
interferons
Natural products discovered in 1957; assist the immune response:
interferons
List the three ways in which interferons function as broader spectrum antivirals:
- inhibit viral replication within host cells
- activate natural killer cells and macrophages
- increase antigen presentation to lymphocytes
Effects of interferon therapy include:
fatigue, fever, myalgias
Interferon therapy was formerly the main treatment for ____ and used for ____.
HCV; HBV
A purine nucleoside analog that inhibits many RNA viruses and some DNA viruses:
Ribavirin
Ribavirin (a purine nucleoside analog) may be used to treat:
- influenza A and B
- measles
- respiratory syncytial virus