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PHA 411 > Antivirals > Flashcards

Antivirals Flashcards

1
Q

What are viruses?

A

Viruses are the smallest living microorganism measuring 20 – 30 nm in size and cannot reproduce outside their host cells, which are usually larger, including bacteria and human cells.

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2
Q

What are virions?

A

A virion is the free-living virus particle outside the host cells.

It consists of nuclear material (RNA or DNA)
enclosed in a protein coat known as capsid which may also be surrounded by an external lipoprotein envelope.

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3
Q

Classification of viruses

A
  1. DNA Viruses
  2. RNA viruses
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4
Q

Examples of DNA Viruses

A

C-H-E-A-P-H-P-V

Cytomegalovirus
Herpesviruses (Shingles, cold sores, glandular fever)
Epstein-Barr virus
Adenovirus (sore throat, conjunctivitis)
Papillomavirus (warts)
Hepatitis B virus,
Poxvirus (smallpox)
Varicella zoster virus (chicken pox)

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5
Q

Examples of RNA viruses

A

A2-P2-R3-HOE

Arboviruses (Yellow fever)
Arenavirus (meningitis, Lassa fever)
Paramyxovirus (measles, mumps, respiratory tract infections)
Picornaviruses (poliomyelitis)
Retroviruses (HIV/AIDS, T-cell
leukemia)
Rhabdoviruses (rabies)
Rubella virus (German
measles)
Hepatitis C virus
Orthomyxovirus (influenza A, B and C)
Enterovirus

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6
Q

Is HPV a DNA or RNA virus?

A

DNA virus

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7
Q

What drugs are used to treat HPV?

A

None.

It is asymptomatic or presents as warts that can be removed using cryotherapy, electrodessication, laser
surgery

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8
Q

What is the replication process of DNA viruses?

A
  1. Viral DNA enters the host cell nucleus, where transcription into mRNA occurs, catalyzed by the host cell RNA polymerase.
  2. Translation of the mRNA into virus-specific proteins then takes place.

Some of these proteins
are enzymes that synthesize more viral DNA, as well as
proteins comprising the viral coat and envelope.

  1. After assembly of coat proteins around the viral DNA, complete virions are released by budding or after host cell lysis.
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9
Q

What is the replication process of RNA viruses?

A
  1. Enzymes within the virion synthesize its mRNA from the viral RNA template, or sometimes the viral
    RNA serves as its own mRNA.
  2. The mRNA is translated by the host cell into various enzymes, including RNA polymerase (which
    directs the synthesis of more viral RNA), and also into
    structural proteins of the virion.
  3. The viral structural proteins are arranged around the newly
    formed viral RNA to form new virions, which escape by
    budding or cell lysis.
  • The nucleus is usually not involved in RNA viral replication except for orthomyxoviruses
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10
Q

What is the replication process of retrovirus?

A
  1. They contain reverse transcriptase enzyme (virus, 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 by integrase enzyme to form a provirus, which is transcribed into both new viral RNA &
    mRNA.
  3. The mRNA is translated into inactive proteins, which are broken down by protease enzymes into structural proteins, followed by assembly.
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11
Q

Why are some viral infections periodical?

A

This is because ability of several viruses are able to remain dormant within, and be replicated together with, the host genome.

when
viral replication is reactivated by some factor (or
when the immune system is compromised, infection reoccurs.

e.g., Varicella zoster (Chicken pox), Herpes labialis (cold sores)

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12
Q

Host defences against viruses

A
  1. Intact skin
  2. Innate and adaptive immune response (T-lymphocytes)
  3. Natural killer cells (mother Turkey strategy)
  4. Gene silencing (viral DNA phosphorylation)
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13
Q

Viral evasion of host defences

A
  1. Subversion of the immune response. e.g., Poxviruses, Cytomegalovirus, Epstein-Barr virus, Adenovirus and herpesviruses
  2. Evasion of immune detection and attack by cytotoxic lymphocytes and NK cells
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14
Q

How do viruses subvert immune response?

A
  1. Some viruses
    express proteins that mimic the extracellular ligand binding domains of the cytokines (interleukin-1, TNF-alpha, antiviral interferons).
  2. The proteins act as pseudo receptors and bind these cytokines, preventing them from reaching their natural receptors, thereby avoiding their destruction of the viral infected cells.
  • They use decoys.
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15
Q

How do viruses evade immune detection?

A
  1. Inhibition of generation of antigenic peptide which normally combines with MHC to form identifiable complex. i.e., they don’t trigger an immune response.
    e.g., adenovirus, cytomegalovirus, Epstein-barr virus &
    herpesvirus.
    (stealth)
  2. Interference with apoptotic pathway. e.g., Adenovirus, cytomegalovirus, Epstein-barr virus.
    (bulletproof)
  3. Adopting the baby turkey ploy. Some viruses hoodwink NK cells by expressing homologue of MHC class 1 molecules.
    (camouflage)
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16
Q

Do antiviral drugs destroy viruses?

A

No. They only inhibit their development or reproduction.

17
Q

Antiviral drugs vs Viricides

A

Antivirals are drugs used in treating viral infections.

Viricides are chemicals that
destroy virus particles. They are not medication. e.g., Lysol, sodium hypochlorite, benzalkonium chloride, essential oils

18
Q

Classification of Non-retroviral antiviral
drugs

A

1) Viral DNA Polymerase Inhibitors
2) Viral neuraminidase Inhibitors
3) Viral coat disassembly Inhibitors
4) NSE protease inhibitors

19
Q

Examples of DNA polymerase inhibitors

A

Cidofovir
Idoxuridine
Ganciclovir
Acyclovir
Ribavirin
Foscarnet
Penciclovir
Valaciclovir
Valganciclovir

C-I-G-A-R F-P-V2

20
Q

Uses of DNA polymerase inhibitors

A
  1. Treatment of herpes infections.
  2. Cidofovir, valaciclovir, ganciclovir and valganciclovir are also used for the treatment of cytomegalovirus infections
  3. Ribavirin is used for the treatment of respiratory syncitial infections, lassa fever and hepatitis c
21
Q

Viral DNA polymerase inhibitors mechanism of action

A
  1. Aciclovir, valaciclovir and
    penciclovir are guanosine analogues that are first converted to the monophosphate by thymidine kinase by the viral enzyme (more rapid) or by the host enzyme.
  2. They are then converted by the host kinases to their triphosphates, which compete with host natural guanosine triphosphate for incorporation into viral DNA chain by the enzyme viral DNA polymerase.
  3. This leads to chain termination and suppression of viral DNA replication.
22
Q

Mechanism of action of Ribavirin

A

Ribavirin is a synthetic nucleoside analogue that is thought to act by altering the viral nucleotide pool or by interfering with the synthesis of viral mRNA.

23
Q

Mechanism of action of foscarnet

A

Foscarnet is a non nucleoside analogue of pyrophosphate which inhibit viral DNA polymerase by binding to the pyrophosphate binding site.

24
Q

Examples of neuraminidase inhibitors

A

oseltamivir, zanamivir, laninamivir &
peramivir

25
Q

Uses of neuraminidase inhibitors

A

Treament of influenza A and influenza B viral infections

26
Q

Neuraminidase inhibitors can be used at any stage of the infection.

True or False

A

False.

They are only effective in the early stages of the infections

27
Q

Mechanism of action of neuraminidase inhibitors

A

Neuraminidase is an enzyme on the surface of the virion that is responsible for severing the bond between the viral coat and the host sialic acid (neuraminic acid).

The neuraminidase inhibitors prevent the escape of the newly replicated viruses by inhibiting the viral neuraminidase.

28
Q

Side effects of neuraminidase inhibitors

A

GIT symptoms such as nausea, vomiting, dyspepsia and diarrhoea.

29
Q

Examples of viral coat disassembly inhibitors

A

Amantadine & rimantadine

30
Q

Uses of viral coat disassembly inhibitors

A

Treatment of influenza A viral
infection

31
Q

Viral coat disassembly inhibitors can treat all influenza infections.

True or False

A

False.

They can only treat influenza A infections

32
Q

Mechanism of action of coat disassembly inhibitors

A

In order for the viral RNA genome to be released in the host cell for replication, the coat disassembly is promoted by an influx of H+ ions through the M2 ion channel that acidifies the viral particle in the host cell cytoplasm.

Amantadine blocks the M2 ion channel

33
Q

Side effects of coat disassembly inhibitors

A

dizziness, slurred
speech and insomnia

34
Q

Example of NSE protease inhibitors

A

Asunaprevir, boceprevir, grazoprevir,
paritaprevir, simeprevir and telaprevir

35
Q

Mechanism of action of NSE protease inhibitors

A

Inhibit viral NSE protease
enzyme which converts large inactive protein/polypeptide (formed after translation from mRNA) to smaller active functional and structural protein.

PHA 411 (6 decks)

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