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PMCOL 200 > 25 Antivirals > Flashcards

25 Antivirals Flashcards

1
Q

What are viruses?

A

Obligate intracellular parasites

  • Rely on host biosynthetic machinery to reproduce
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2
Q

Viruses that are not inside an infected cell exist as __________

A

Viruses that are not inside an infected cell exist as independent particles (Virions)

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3
Q

What do virions consist of?

A
  • Double or single stranded DNA or RNA
  • A protein coat (capsid)
  • Some have a lipid envelope derived from the host cell - may contain antigenic glycoproteins
    • often important in helping virus integrate/attach onto the host cell
  • ~1/100th the size of the average bacterium
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4
Q

The capsid (protein coat) and lipid envelope of a virion may contain antigenic glycoproteins. What purpose do these glycoproteins have?

A

often important in helping virus integrate/attach onto the host cell

  • antigens bind to receptors in the host that allow it to attach/integrate
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5
Q

What is the Viral Range?

A

Group of cell types or species that a virus can infect

eg (HIV affects only T-Cells)

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6
Q

What is a bacteriaphage?

A

Virus that infects only bacteria

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7
Q

Most animal viruses do not cross ______ and some only infect closely related ______

A

Most animal viruses do not cross phyla and some only infect closely related species

  • eg humans and primates for poliovirus
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8
Q

What are the three shape-based classifications of viruses?

A
  1. Helical
    • eg rabies, tobacco mosaic virus
  2. Icosahedral
    • herpes simplex virus, poliovirus
  3. Complex
    • smallpox viruses
    • bacteriophages
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9
Q

Define pathogenicity

A

Ability of viruses to cause disease

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10
Q

Define virulence

A

The degree of pathogenicity (ability of viruses to cause disease)

ie how bad the disease is that’s associated with the viral infection

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11
Q

What is latency?

A

Some viruses can remain dorman in organisms = latency

eg chickenpox, shingles (varicella-zoster remains dormant in dorsal root ganglia => shingles)

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12
Q

People chronically infected are called _____ and serve as reservoirs of infectious virus

A

People chronically infected are called carriers and serve as reservoirs of infectious virus

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13
Q

What are the four stages of a virus “life”-cycle?

A
  1. Absorption
  2. Penetration
  3. replication
  4. release
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14
Q

How do viruses bind to receptor proteins on host cell?

A

Along the capsid (surface of virus) there are glycoproteins that bind to specific receptors on host cell

  • binding mediates adhesion of virion to host
  • interaction determines the host range of a virus and begins the infection process
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15
Q

What is (viral) penetration?

A

After virus is bound to host receptors, Viral DNA or RNA crosses the plasma membrane to the cytoplasm or nucleus

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16
Q

Once inside the host cell, what is the action of the viral DNA/RNA?

A

Viral DNA or RNA interacts with host machinery for translating DNA or RNA into viral protein (Replication)

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17
Q

Following replication, what happens to the newly synthesized virion particles?

A

Packaged and released into the environment to continue the infection process

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18
Q

The viral RNA or DNA can be _______ or _______ and is eventually converted into ______

A

The viral RNA or DNA can be single-stranded or Double-stranded and is eventually converted into mRNA and then eventually into protein using the host machinery (enzymes) used to translate/transcribe

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19
Q

DNA viruses are generally _________ (double or single?) and enter the host cell ______

A

DNA viruses are generally double-stranded (double or single?) and enter the host cell nucleus

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20
Q

What happens after DNA viruses enter the host cell nucleus?

A
  • Viral DNA is integrated into the host genome
    • transcribed into mRNA by host DNA-dependent RNA polymerase
    • mRNA is translated into virus-specific proteins (DNA → RNA → protein)
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21
Q

What is responsible for transcribing viral DNA into mRNA?

A

Host DNA-depended RNA polymerase

(host enzymes)

RNA is then translated into viral protein

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22
Q

In addition to making viral protein, the virus also wants to replicate its genome. What does this require?

A

Viral genome replication requires DNA-dependent DNA polymerase from the host or virus

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23
Q

DNA viruses rely on enzymes within the nucleus of the host cell for both ______ and _______

A

DNA viruses rely on enzymes within the nucleus of the host cell for both transcription and replication

  • Transcription:
    • DNA-dependent RNA polymerase
  • Replication
    • DNA-Dependent DNA polymerase
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24
Q

How are Pox viruses different from other DNA viruses?

A

Poxviruses carry their own DNA-dependent RNA polymerase and replicate in the host cell cytoplasm

  • Carrying their own enzyme allows them to replicate in the cytoplasm
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25
Q

Double-stranded RNA viruses require __________ (must make itself)

A

Double-stranded RNA viruses require RNA-dependent RNA polymerases (must make itself) (RNA → mRNA)

  • RNA to mRNA never happens in eukaryotic cells so there isn’t an enzyme for that
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26
Q

The viral RNA-depended RNA polymerase acts both as a _______ and a _________

A

The viral RNA-depended RNA polymerase acts both as a transcriptase and a replicase

  • Transcriptase:
    • transcribe mRNA
  • Replicase
    • replicate the viral genome
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27
Q

Most RNA viruses complete their replication in the host cell _______ but some, such as influenza are transcribed in the host cell _______

A

Most RNA viruses complete their replication in the host cell cytoplasm but some, such as influenza​ are transcribed in the host cell nucleus

  • don’t require any host transcription enzymes = don’t need to get into the nucleus
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28
Q

What are retroviruses?

A

Retroviruses have an RNA genome that directs the formation of a DNA molecule

(RNA → DNA → mRNA → protein)

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29
Q

In retroviruses, the viral enzyme _______ copies viral RNA into DNA (therefore it is a _____________ enzyme)

A

In retroviruses, the viral enzyme reverse transcriptase copies viral RNA into DNA (therefore it is a RNA-dependent DNA polymerase enzyme)

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30
Q

What happens to the DNA that is created from the RNA of the retrovirus (via reverse transcriptase)

A

The resulting viral DNA is integrated into the host DNA (then transcribed into mRNA and translated into protein by host enzymes)

31
Q

Most retroviruses do not immediately kill their host cell. Instead, they?

A

Most retroviruses do not immediately kill their host cell. Instead, they continue to replicate producing daughter cells with integrated proviral DNA = result in latent infections that can last for many years (eg HIV)

32
Q

What enzyme do retroviruses have to supply themselves (ie what enzyme do they require that host cells do not have)?

A

Reverse transcriptase (RNA-dependent DNA polymerase)

  • Euk cells do not make DNA from RNA therefore wouldn’t need such an enzyme
33
Q

What is the best and cheapest way to treat viral infection?

A

Through prevention (largely through Vaccination programs)

34
Q

Vaccines can consist of _________ or _______ viruses OR ________ or ________

A

Vaccines can consist of live-attenuated (can’t replicate) or killed viruses OR viral proteins or mRNA (antigens) = stimulates immune response to produce antibodies

35
Q

Not all viral infections have vaccines, and therefore, ______ have been created to manage the infection after they occur

A

antivirals

36
Q

Anti-viral drugs can exert actions at several stages of viral replication including:

  • _________
  • _________
  • ________
  • _________
  • _________
A

Anti-viral drugs can exert actions at several stages of viral replication including:

  • Viral entry
  • Nucleic acid synthesis
  • Protein synthesis
  • Viral packaging
  • Virion release
37
Q
A
38
Q

What are two pros of combination therapy?

A
  1. Can result in greater clinical effectiveness against viral infections
  2. Prevent or delay the emergence of resistance
39
Q

Anti-viral drugs are Virustatic. What does this mean?

A

Only active against replicating viruses and do not affect latent virus

  • Basically, we have no drugs that kill a dormant virus
40
Q

To what class of Anti-viral drug does acyclovir belong?

A

Anti-herpes drugs

41
Q

What is acyclovir?

A
  • Anti-herpes anti-viral
  • Nucleoside analog (fake DNA binding block)
    • Viruses incorporate into their genomes during replication
    • Lacks a hydroxyl group important for forming the backbone

= DNA chain termination

42
Q

What feature of nucleosides does acyclovir lack?

A

Acyclovir lacks a hydroxyl group

  • Hydroxyl group is important for attachment to the next nucleoside
  • w/o the hydroxyl group = DNA chain termination
43
Q

Why does acyclovir only halt viral DNA replication and not interfere with host cell DNA replication?

A

Acyclovir must be phosphorylated to acyclovir-triphosphate to be incorporated into viral DNA as a terminal substrate

  • the first phosphate group is added by the herpes simplex virus (herpes)-thymidine kinase which has an affinity for acyclovir that is 200x that of mammalian enzyme (thymidine kinase)
    • greater specificity
44
Q

What can acyclovir resistance in herpes simplex virus result from?

A
  • Impaired production of viral thymidine kinase
    • Virus down-regulate activity of viral thymidine kinase = less efficient at converting acyclovir to acyclovir monophosphate
  • Altered thymidine kinase substrate specificity
    • Eg phosphorylation of thymidine but not acyclovir
  • Altered viral DNA polymerase
45
Q

What is a lentivirus? Give an example

A

Lentivirus = Family of retroviruses that lead to chronic persistent infection with gradual onset of clinical symptoms

Eg: HIV (human immunodeficiency virus)

46
Q

What cell type does HIV infect?

A

HIV infects human immune cells (CD4+ T-cells)

47
Q

What happens with CD4+ T-cells decline below a critical level?

A

Cell mediated immunity is lost and the body becomes susceptible to opportunistic infections (AIDS)

-can be fatal

48
Q

In the absence of tx, what does replication of the HIV look like?

A

Replication is constant following infection in the absence of treatment

  • No true period of viral latency following infection
49
Q

Anti-viral HIV drugs target viral infection at multiple levels, these include:

A
  • Fusion
  • Transcription
  • Integration into host genome
  • Virion release
50
Q

Current HIV tx usually involves ____ antiretroviral drugs

A

Current HIV tx usually involves 3+ antiretroviral drugs

51
Q

What is Highly active antiretroviral therapy (HAART)?

A

Drug combinations (usually target multiple steps along pathway) that can slow or reverse the increases in viral RNA load that normally accompany progression of disease

52
Q

What characteristic of HIV infection are the Entry-inhibitor anti-virals based on?

A

HIV infection begins with attachment of HIV envelope proteins called gp120 to CD4 and CCR5 receptors on surfaces of T-cells

  • Entry inhibitors interfere with binding, fusion and entry of an HIV virion into a human cell
53
Q

Provide an example of an entry-inhibitor

A
  • Maraviroc is a CCR5 receptor antagonist (interferes with HIV binding to T-cell)
    • Anti-viral for HIV
54
Q

What receptors on T-cells do the HIV envelope proteins (gp120) bind to?

A

CD4 and CCR5 receptors

(co-receptors = usually found together)

55
Q

What are Nucleoside Reverse Transcriptase Inhibitors (NRTI)

A
  • Antiviral for HIV
  • Resembles the nucleoside building blocks used to make DNA (similar to acyclovir in the tx of herpes)
  • Incorporated into new HIV DNA chains but lack the 3’OH = chain termination
56
Q

What characteristic of HIV allows nucleoside reverse transcriptase inhibitors to work?

A
  • HIV reverse transcriptase enzyme synthesizes DNA from HIV RNA using nucleosides in the host T-cell (RNA dependent DNA polymerase
  • Adding NRTI (fake analog nucleoside) halts the DNA chain
    • similar to action of acyclovir in tx or herpes
57
Q

Why don’t NRTI’s inhibit mammalian (host-cell) transcription?

A

Mammalian RNA and DNA polymerases are sufficiently distinct to permit a selective inhibition of viral reverse transcriptase

58
Q

What are Integrase Strand Transfer Inhibitors (INSTs)?

A
  • Antivirals for HIV
  • Integrase in a viral enzyme that inserts viral genome into the DNA of the host cell
  • Integrase inhibitors block the action of integrase to inhibit HIV proliferation
  • Eg Raltegravir
59
Q

What is Raltegravir?

How does Raltegravir work?

A

Raltegravir is an integrase strand transfer inbitor for the tx of HIV

  • Blocks the action of the viral enzyme integrase to prevent the insertion of viral genome into the host cell
60
Q

What are protease inhibitors?

A
  • Antiviral used to treat HIV
  • Targets last step of viral life cycle (release of new virions)
61
Q

Assembly of infectious HIV virions is dependent on _______

A

Assembly of infectious HIV virions is dependent on aspartate proteases

62
Q

What do aspartate proteases do?

A

Aspartate proteases are viral enzymes that cleave precursor proteins to form the final structural proteins of the mature virion core

63
Q

HIV protease inhibitors are designer drugs based on molecular characterization of the __________

A

HIV protease inhibitors are designer drugs based on molecular characterization of the active site of the viral enzyme

  • Inhibits ability of aspartate proteases
  • Block new HIV from becoming mature, virulent HIV
64
Q

Protease inhibitors are usually used in combination with?

A

Reverse transcriptase inhibitors

65
Q

What is amantadine?

A

Anti-influenza drug

66
Q

What is the target of amantadine?

A

Amantadine targets (and inhibits) the early step in replication (viral uncoating) of the influenza A virus

67
Q

When the influenza virus binds to the host cell it is integrated into the cytoplasm. In order for the genetic material to escape the viral capsid and integrate into the host nucleus, the viral particle must be acidified. What protein allows this?

A

M2 protein functions as a proton ion channel required at the onset of infection to permit acidification of the virus core which in turn activates viral RNA transcriptase

68
Q

Acidification of the virus core activates _______

A

RNA transcriptase

69
Q

What is the action of amantadine?

A

Amantadine blocks proton transfer through M2, blocking acidification and the initiation of viral transcription

  • Anti-influenza A
70
Q

Amantadine is prophylactive against _________ infection

A

Influenza A (not B)

And can reduce duration of symptoms if given within 48 hours of contact

  • Not as effective as vaccines
71
Q

What is an alternative to vaccination in high risk patients?

A

Seasonal prophylaxis using anti-virals

72
Q

What are neuroaminidase (neuraminidase) inhibitors?

Example?

A

Class of anti-influenza drugs

Eg Zanamivir

73
Q

What is the action of neuroaminidase (neuraminidase) inhibitors?

A
  • Neuroaminidases are produced by influenza A and B
    • Cleave sialic acid residues from viral proteins that enable virus to be released from the host cell
  • Inhibition of this helps prevent viral spread
74
Q

Neuroaminidases (neuraminidases) cleave ________ from viral proteins that enables the virus to be ______

A

Neuroaminidases cleave sialic acid residues from viral proteins that enable the virus to be released from host cell

PMCOL 200 (30 decks)

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