Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Microbiology And Immunology > Mechanism Of Antivirals** > Flashcards

Mechanism Of Antivirals** Flashcards

You may prefer our related Brainscape-certified flashcards:
Biology 101 flashcards
1
Q

What do antibiotics and anti-virals treat?

A
  • Antibiotics = Treat bacteria
  • Anti-virals = Treat virus
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Why do we need anti-viral drugs?

A
  • There are no or poorly effective vaccines for some viruses important to human health.
  • Not everyone can be administered a vaccine, even if that vaccine is effective.
  • Immune response to vaccine administration can take time and several sequential administration
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

State examples of infections or disease that require anti-viral drugs?

A
  • Acute infection (“Quick killers”) e.g. influenza; ebola; MERS; SARS
  • Chronic infection disease: hepatitis B [350,000,000 carriers], hepatitis C [200,000,000 carriers], human papilloma viruses, [cervical cancer, second commonest cancer in women]
  • Human immunodeficiency virus (HIV): [40 million infected]
  • Acute inflammatory e.g. herpes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

State current uses of anti-viral drugs with examples of infections or diseases and the agent used (5)?

A

Standard infection
• Treatment of acute infection
• Influenza; Chickenpox; herpes infections - (aciclovir)
• Treatment of chronic infection:
- HCV, HBV, HIV (numerous different agents)

Prophalyxis
• Post-exposure prophylaxis and preventing infection:
- HIV (PEP)
• Pre-exposure prophylaxis: HIV (PrEP)
• Prophylaxis for reactivated infection: e.g. in transplantation - CMV (ganciclovir, foscarnet)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

How do we induce ‘selective toxicity’ in anti-viral drugs as therapeutic agents?

A
  • Selective toxicity = Inhibits virus replication without harming infected cell
  • Occurs by
  • Target protein in virus, not infected cell (if possible)
  • Due to the differences in structure and metabolic pathways between host and pathogen
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

State the 9 general steps within the virus life cycle?

A
  1. Recognition
  2. Attachment
  3. Penetration
  4. Uncoating
  5. Transcription
  6. Protein synthesis
  7. Replication
  8. Envelopment
  9. Budding and release
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

State the 5 modes of action of selected anti-virals?

A
  • Preventing virus adsorption onto host cell
  • Preventing penetration
  • Preventing viral nucleic acid replication (nucleoside analogues)
  • Preventing maturation of virus
  • Preventing virus release
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

State common enzyme targets from anti-viral drugs and why?

A
  • Thymidine kinase and HSV/VZVICMV
  • Protease of HIV
  • Reverse transcriptase of HIV
  • DNA polymerases
  • Neuraminidase of influenza virus
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Why is it so difficult to develop effective, non-toxic, anti-viral drugs? (8)

A
  • Viruses use cellular proteins which may have other functions
  • Viruses must replicate inside cells - obligate intracellular parasites
  • Viruses take over the host cell replicative machinery
  • Viruses have high mutation rate - quasispecies
  • Anti-virals must be selective in their toxicity i.e. exert their action only on infected cells
  • Some viruses are able to remain in a latent state e.g. herpes, HPV
  • Some viruses are able to integrate their genetic material into host cells e.g. HIV
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What viruses does aciclover target and specifically what treatments does it cover?

A
  • Targets herpes virus (commonly characterised via muco-cuntaneous lesions - cold sores)
  • Herpes viruses include: • Herpes simplex (HSV), • Varicella Zoster Virus (VZV) • Cytomegalovirus (CMV) • Epstein-Barr virus (EBV)
  • Adminstered via IV/oral/tropical
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What treatments does herpes simplex virus cover?

A
  • Treatment of encephalitis
  • Treatment of genital infection
  • Suppressive therapy for recurrent genital herpes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What treatments does CMV/EBV cover?

A

Prophylaxis only

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What treatments does Varicella Zoster Virus cover?

A
  • Treatment of chickenpox
  • Treatment of shingles
  • Prophylaxis of chickenpox
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What virus does ganciclovir, foscarnet and cidofovir target in relation to aciclover?

A
  • Link between these are they all target herpes virus, but aciclover doesn’t excusively target CMV like these drugs do
  • Herpes viruses include: • Herpes simplex (HSV), • Varicella Zoster Virus (VZV) • Cvtomegalovirus (CMV) • Epstein-Barr virus (EBV)
  • ganciclovir: IV/oral, For CMV
  • Foscarnet: IV/local application, For CMV
  • Cidofovir: IV for CMV
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Describe the selective toxicity of aciclover mechanism with the enzymes involved?

A
  • Aciclover is activated to active drug within infected cell
  • Requires 2 viral enzymes:
  • Thymidine kinase (TK) = selectively activates ACV via phosphorylation to ACV triphophostae (activated drug)
  • DNA polymerase = Selectively inhibited via drug
  • Overall account for low toxicity of drug
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Why is aciclovir so effective and safe?

A
  • HSV thymidine kinase (TK) has 100x the affinity for ACV compared with cellular phosphokinases
  • Acyclovir triphosphate has 30x the affinity for HSV DNA polymerase compared with cellular DNA polymerase.
  • Acyclovir triphosphate is a highly polar compound - difficult to leave or enter cells (but aciclovir is easily taken into cells prior to phosphorylation)
  • DNA chain terminator
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

State the uses of ganiclovir in CMV (3)

A
  • Reactivated infection or prophylaxis in organ transplant recipients
  • Congenital infection in newborn
  • Retinitis in immunosuppressed
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Describe briefly the mechanism of action of ganiclover? VD

A
  • Active for CMV
  • Structurally similar to aciclovir
  • CMV does not encode TK but has UL97 kinase
  • Inhibits CMV DNA polymerase
19
Q

Describe the uses of Foscarnet

A
  • Used for CMV infection in the immunocompromised e.g. pneumonia in solid organ and bone marrow transplants.
  • May be used because of ganciclovir resistance (TK mutants)
20
Q

Describe the mechanism of action for foscarnet

A
  • Mechanism of action
  • Selectively inhibits viral DNA/RNA polymerases and RTs
  • No reactivation required
  • Binds pyrophosphate binding site - a structural mimic
21
Q

Describe the uses of cidofovir

A
  • Drug active against CMV; but MUCH MORE nephrotoxic
  • Treatment of retinitis in HIV disease
22
Q

Describe the mechanism of action for cidofovir

A
  • Mechanism of action
  • Chain terminator
  • Targets DNA polymerase
  • Competes with dCTP
  • Monophosphate nucleotide analog
  • Prodrug - phosphorylated by cellular kinases to di-phosphate
23
Q

Describe how resistance to anti-virals in herpes viruses occur?

A
  • Two main mechanisms
  • Thymidine Kinase mutants
  • DNA polymerase mutants
  • If occurs in TK, drugs not needing phosphorylation are still effective (e.g. foscarnet, cidofovir)
  • If occurs in DNA polymerase, all drugs rendered less effective
  • VERY RARE in immune competent patients (low viral load) - less likely for viral mutants to arise
24
Q

Label the structural features of HIV from this diagram (make anki card for this manually)

A
  • Envelope protein, g120 with transmembrane gp41
  • Membrane associated matrix protein Gag 17
  • Nucleocapsid protein Gag 24
  • ds RNA genome
  • Viral envelope
  • Reverse transcriptase
25
Q

State the 7 steps within the life cycle of HIV?

A
  1. Attachment with binding of viral gp120 via CD4 and CCRX
  2. reverse transcription of RNA into dsDNA
  3. Integration into host chromosome of proviral DNA
  4. Transcription of viral genes
  5. Translation of viral mRNA into viral proteins
  6. Virus assembly and release by budding
  7. Maturation
26
Q

State the common targets for inhibitors of anti-HIV drugs (4)

A
  1. Anti-reverse transcriptase inhibitors: nucleoside/nucleotide RT inhibitors, non-nucleotide RT inhibitors (allosteric)
  2. Protease inhibitors - multiple types
  3. Integrase inhibitors - POL gene: Protease, reverse transcriptase and integrase (IN) with the 3 ‘end encoding for IN (polynucleotidyl transferase)
  4. Fusion inhibitors - gp120/41 - biomimetic lipopeptide
27
Q

State the key treatment for HIV?

A
  • Highly Active Anti Retroviral Therapy
  • HAART Combination of drugs to avoid resistance
28
Q

Describe the mechanism of action behind nucleoside reverse transcriptase (NRTIs) inhibitors and state one example?

A
  • Example: AZT-zidovudine
  • Synthetic analogue of nucleoside thymidine - when converted to tri-nucleotide by cell enzymes, it blocks RT by (competitive inhibitor):
  • Competing for natural nucleotide substrate dTTP
  • Incorporation into DNA causing chain termination
  • Others ddl, ddC, d4T, and 3TC (2’3’-dideoxy-3’-thiacytidine )???
29
Q

Describe the mechanism of action behind non-nucleoside reverse transcriptase (NNRTIs) inhibitors and state one example?

A
  • Example: Nevirapine
  • Mechanism:
  • Non-competitive inhibitor of HIV-1 RT -> terminates production of new viral genomes (don’t need to write this)
  • Synergistic with NRTI’s such as AZT because of different mechanism
  • Allows for resistance to occur
30
Q

How does NNRTI’S and NRTI’s differ from one another?

A

The NNRTIs differ from the NRTIs in that they do not have a nucleotide structure and do not depend on phosphorylation for activity.

31
Q

Describe the treatment for pre- (PrEP) and post-exposure
prophylaxis treatment for HIV?

A
  • PEP - within 72 hours post exposure: Take for 28 days. 2x NRTIs + integrase inhibitor
  • PrEP - pre-exposure - blocks transmission
  • 2x NRTIs (Truvada)
  • two tablets 2 - 24 hours before sex, one 24 hours after intercourse and a further tablet 48 hours after intercourse - called ‘on-demand’ or ‘event based’ dosing
  • 2 × NRTIs = Combination of Nucleoside RTIs emtricitabine (guanosine analog) + tenofovir (adenosine analog)
32
Q

Describe how resistance to anti-virals can occur?

A
  • Use of single agents leads to rapid development of resistance
  • Causes the drug binding site is altered in structure by as few as one amino acid substitution
  • If Mutation rate - high + Viral load - high (like HIV) -> resistance
33
Q

How does HIV become resistant to anti-virals and describe how this can occur?

A
  • Selection pressure and mutation frequency •
  • Increased mutation rate seen in HIV. •
  • They form a quasispecies within an individual patient:- A viral swarm (large number of different HIV viruses each with different genome content)
  • The error rate in copying viral genome by reverse transcriptase enzyme is 1 base per 10 4-5 incorporations; lacks proof reading capacity. So, for HIV with 10 9-10 viruses produced every day, ALL possible viral variants would be produced (due to large error rate)
  • Hence use of combinations of antivirals e.g. HAART
34
Q

State 3 drugs that can be used to treat influenza with mechanism stated?

A
  • Amantadine: Inhibit virus uncoating by blocking the influenza encoded M2 protein when inside cells and assembly of haemagglutinin. Now rarely used
  • Zanamivir and Oseltamivir (Tamiflu): Inhibits virus release from infected cells via inhibition of neuraminidase Oseltamivir -oral, Zanamivir- inhaled or IV - less likely for resistance to develop
35
Q

Describe and state 2 examples and the mechanism of action of anti-flu drugs and the type of inhibitor they are?

A
  • Anti’flu agents - Relenza - (zanamivir) and Tamiflu - (oseltamivir)
  • Target and inhibit NA at highly conserved site (reduce chances of resistance via mutation)
  • Prevent release of sialic acid residues from the cell receptor
  • Preventing virus budding and release and spread to adjacent cells
  • NA = Neuraminidase inhibitors
36
Q

State the mechanism and use of ribavirin?

A
  • Ribavirin : nucleoside analogue
  • Block RNA synthesis by inhibiting inosine 5’ monophosphate (IMP) dehydrogenase - this blocks the conversion of IMP to XMP (xanthosine 5’-monophosphate) and thereby stops TP synthesis and, consequently, RNA synthesis
  • Treat: RSV and HepC (in combination with pegylated interferon
37
Q

State the use of direct-acting antivirals (DAAs) in what disease and how it affects it?

A
  • relatively new class of medication •
  • Acts to target specific steps in the HCV viral life cycle •
  • Shorten the length of therapy, minimize side effects, target the virus itself, improve sustained virologic response (SVR) rate.
  • Structural and non-structural proteins - replicate and assemble new virions
  • HCV - first chronic viral infection to be cured without IN or ribavirin.
38
Q

Describe the targets of Direct A-acting Antivirals in HCV?

A
  • All the major HCV-induced enzymes - NS2-3 and NS3-4A proteases, NS3 helicase and NS5B RNA-dependent RNA polymerase (RdRp) are essential for HCV replication and are potential drug targets.
  • DAA with different viral targets, are synergistic in combinations
39
Q

State exposure prone incidents and the prevention and management in occupational infection hazards?

A
  • Exposure prone incidents : Sharps, Splashes and blood-born viruses
  • Prevention - Universal Precautions
  • Management: Emergency Management of exposure prone incidents
40
Q

Describe the post-exposure prophyaxlis treatment for Hep B?

A
  • Нер B
  • Specific Hep B immunoglobulin (passive immunity) + vaccination within 48 hours (HBV treatment includes antivirals 3TC/NRTIs)
41
Q

Describe the post-exposure prophyaxlis treatment for Hep C?

A
  • Interferon-gamma + ribavarin (anti-viral) for 6 months within first 2 months of exposure 90% cure rate
  • Now direct acting antivirals
42
Q

Describe the post-exposure prophyaxlis treatment for HIV?

A
  • HIV
  • 80% protection i.e. no sero-conversion must be FAST - hours antiviral drug treatment - 28 days 2xNRTI + protease or integrase inhibitor
43
Q

State examples of viral infection with no effective therapies (6)?

A
  • Rabies virus
  • Dengue
  • Common cold viruses
  • Ebola
  • HPV
  • Arbovirsues

Microbiology And Immunology (32 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions