Antivirals Flashcards
Describe the structure of viruses.
• Viruses are small infective agents consisting essentially of nucleic acid (RNA or DNA) enclosed in a protein coat (capsomeres). Can potentially be enveloped.
What does it mean when we say that viruses are obligate intracellular parasites ?
They have to use the metabolic processes of the host cell (since they have no metabolic machinery of their own), which they enter and infect.
Where do some viruses derive their envelope form ?
They pinch some of the plasma membrane of our cells.
Is taxonomy important for viruses ? Why or why not ?
Yes it is, because it dictates treatment (some forms of treatment will work against some types of viruses but not others)
Explain the process of viral replication.
-Basically: Attach to and enter a living host cell-animal, plant or bacterial-and use its metabolic processes.
- The binding sites on the virus are polypeptides on the envelope or capsid. These are receptors which are normal membrane constituents-receptors for cytokines, neurotransmitters or hormones, ion channels, integral membrane glycoproteins, etc.
- Then, with many viruses, the receptor-virus complex enters the cell by receptor-mediated endocytosis during which the virus coat may be removed. Some bypass this route.
- Then, once in the host cell, the nucleic acid of the virus then uses the cell’s machinery for synthesizing nucleic acid and protein and the manufacture of new virus particles.
Identify the main steps in a virus’s life cycle.
- Recognition
- Attachment
- Penetration or Fusion
- Uncoating
- Transcription
- Protein Synthesis
- Replication
- Assembly then lysis and release OR envelopment then budding and release
Identify the main classes of antiviral drugs, explaining which viral process each class interferes with.
- Entry inhibitors: target viral fusion (T20/Enfuvirtide) and a host cell co-receptor (maraviroc)
- Viral uncoating (amantadine/rimantadine)
- Nucleoside anologue chain termination (e.g. Acyclovir, NRTIs)
- NNRTIs (non-nucleoside reverse transcriptase inhibitors) inhibit reverse transcriptase directly (delaviridine, efavirenz)
- Protease inhibitors target the HIV and HCV-encoded protease (Telaprevir and Boceprevir target HCV-encoded protease)
- Integrase Inhibitors (Raltegravir, Elvitegravir and Dolutegravir)
- Virus release inhibitors: influenza NA inhibitors (zanamivir, oseltamivir)
- Immunomodulator PEG-IFN-α
What is immunomodulator PEG-IFN-α used for ?
HCV and HBV treatment
Explain the mechanism of action of protease inhibitors.
- Host mRNAs code directly for functional proteins.
- In HIV, the mRNA is translated into biochemically inert proteins. A virus-specific protease then converts them into various functional proteins.
- Since the protease does not occur in the host, it is a good selective-toxicity target.
Protease inhibitors interfere with the action of those virus-specific proteases
Give examples of DNA viruses.
Herpes Simplex Virus (HSV), Human Papilloma Virus (HPV)
Explain how DNA viruses work.
1) Entry of the viral DNA into the host cell nucleus
2) Transcription of this viral DNA into mRNA by host cell RNA polymerase
3) Translation of the mRNA into virus- specific proteins
What viruses are protease inhibitors used for ?
HCV and HIV
How does aciclovir work to interfere with viral activity/replication ?
Through nucleoside anologue chain termination.
Identify the clinical uses of Aciclovir.
Treatment of herpes simplex virus and varicella zoster virus infections (especially indicated in compromised patients). This includes:
-Genital herpes simplex (treatment and prevention)
-Herpes simplex labialis (cold sores)
-Shingles
-Acute chickenpox in immunocompromised patients
-Herpes simplex encephalitis
-Acute mucocutaneous HSV infections in immunocompromised patients
-Herpes of the eye and herpes simplex blepharitis (a chronic (long-term) form of
herpes eye infection)
-Prevention of herpes viruses in immunocompromised people (such as people undergoing cancer chemotherapy)
Give examples of RNA viruses.
Influenza (Flu), Hepatitis C Virus (HCV)
How are RNA viruses classified ? List the different classes.
RNA viruses classified according to the sense or polarity of their RNA
• Positive-sense viral RNA – is similar to mRNA and can be immediately translated by the host cell.
• Negative-sense viral RNA - is complementary to mRNA and must be converted to positive-sense by an RNA polymerase before translation.
Explain how RNA viruses work.
1) Positive-sense viral RNA immediately translated by the host cell
Negative-sense viral RNA converted to positive-sense by an RNA polymerase then translated
2) RNA polymerase directs the synthesis of more viral genomic RNA
Where does RNA virus and DNA virus replication occur ?
DNA replication - nucleus
RNA replication - cytoplasm
Give examples for Retroviruses.
HIV, Human T cell Leukemia Virus (HTLV)
How do retroviruses work ?
1) The virus contains reverse transcriptase (RT) an RNA- dependent DNA polymerase, which makes a DNA copy of the viral RNA.
2) This DNA copy is integrated into the genome of the host cell and it is then termed a provirus
3) The provirus DNA is transcribed into both new genomic RNA and mRNA for translation into viral proteins using host cell machinery.
What is the relation between retroviruses and cancers ?
An example of retrovirus is Human T cell Leukemia; some RNA retroviruses can transform normal cells into malignant cells.
Why is it difficult to eradicate infection due to a retrovirus ?
Because they are not included in the host genome.
Identify the main mechanistic classes of antiretroviral drugs. How many classes and drugs are there for antiretroviral therapy ?
6 classes of drugs, 25 drugs
Reverse Transcriptase (RT) Inhibitors
1) -Nucleoside analogs: abacavir, didanosine
2) -Non-nucleoside analogs: delaviridine, efavirenz
3) Protease (PR) Inhibitors
Telaprevir and Boceprevir
4) Entry Inhibitors
Maraviroc
5) Fusion Inhibitors
Enfuvirtide
6) Integrase (IN) Inhibitors
Raltegravir
