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Microbiology > ExamLec7ViralReplicationandAntiviralDrugs > Flashcards

ExamLec7ViralReplicationandAntiviralDrugs Flashcards

1
Q

What are the stages of the virus life cycle?

A

1.attachment
2.entry
3.uncoating
4.viral gene expression
5.viral genome replication
6.Assembly
7.Budding/egress

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2
Q

explain attachment

A

either specific receptor or general cell surface component

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3
Q

How does the virus attach to host cell

A

via a specific receptor
- protein receptor

or general cell surface component
-carbohydrate moiety
–sialic acid
–heparan sulfate
–proteoglycan

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4
Q

What is the virus attachment protein?

A

protein or glycoprotein
–part of the capsids (non enveloped viruses)
–intergral membrane protein (enveloped viruses)

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5
Q

What is the attachment protein for HIV

A

gp120

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6
Q

What is the receptor molecule for HIV

A

CD4 plus chemokine co-receptor (CCR5 or CXCR4)

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7
Q

What is the attachment protein for influenza

A

hemagglutinin (HA)

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8
Q

What is the receptor molecule for influenza

A

sialic acid

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9
Q

The virus can enter the cell by _______ of the virus envelope with cell membranes (enveloped viruses)

A

fusion

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10
Q

how do enveloped viruses get taken up by the host cell

A

direct fusion

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11
Q

The virus can enter the cell by _____ (most naked viruses)

A

receptor mediated endocytosis

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12
Q

How do naked viruses get taken up the cell

A

endocytosis or receptor mediated

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13
Q

What is uncoating?

A

viral genome is delivered into cell cytoplasm or nucleus

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14
Q

______ genomes travel to the nucleus (expect for poxviruses)

A

DNA virus

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15
Q

_____ genomes remain on the cytoplasm (except for influenza and retroviruses)

A

RNA virus

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16
Q

How do you uncoat a non enveloped virus

A

pumping protons into the phagosome to degrade the capsid

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17
Q

What is viral gene expression?

A

Viral mRNAs are synthesized/ making proteins

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18
Q

In DNA viruses how do they translate

A

use host RNA polymerase

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19
Q

In RnA viruses how do they translate

A

(-) sense RNA: vital RNA dependent RNA polymerase (transciptase)
*** complement mRNA so it needs to be transcribed to get mRNA to be translated

(+) sense RNA: host ribosomal machinery

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20
Q

What is viral genome replication?

A

DNA viruses:
-Small: host DNA polymerase
-Large: viral DNA polymerase

BOTH - and + sense RNA:
viral RNA dependent RNA polymerase (replicase)
*** they need their own RNA pol since body cannot replicate RNA

21
Q

Where are the sites of replication of RNA virus and DNA viruses

A

RNA: cytoplasm

DNA: nucleus

22
Q

What are the two exceptions for the sites of replication of RNA virus and DNA viruses

A

RNA Viruses: Influenza and retroviruses replicate in the nucleus

DNA Viruses: Poxviruses (complex) replicate in the cytoplasm (!!!)

23
Q

What is assembly

A

viral genome and proteins are assembled to form new virions

24
Q

What is budding/egress?

A

Newly synthesized virions leave the host cell and move on to the next cell

25
Q

How do enveloped viruses leave the cell?

A

can bud at the plasm membrane or intracellular membranes IER, Golgi vesicles)

26
Q

How do non enveloped viruses leave the cell

A

usually cause cell lysis

27
Q

What are the two types of attactment- passive immunization antiviral

A

hyperimmune gamma globin

monoclonal antibodies

28
Q

What are examples of hyperimmune gamma globulin

A

CMV (cytogam)
HAV, measles (BayGAM)
HBV (Bayhep B, Nabi-HB)
RSV (respigam)

29
Q

What are examples of monoclonal antibodies

A

RSV (palivizumab, Synagis)L anti-F

ZEBOV (ATO/MAF/ODE, inmazeb): anti-GP

SARS CoV-2 (bebtelovimab, TIX/CIL: anti S (EUA)

30
Q

What are the two types of entry antivirals

A

coreceptor antagonist

fusion inhibitors

31
Q

example the example given for coreceptor antagonist and fusion inhibitors

A

IN HIV:

CoRA: Co-receptor antagonist
–maraviroc, CCR5 inhibitor
–ibalizumab, anti-gp120 Man
** prevent the connection of receptors

FI: fusion inhibitor
- enfuvirtide, gp41 peptide

32
Q

What is an example of uncoating in antiviral

A

ion channel inhibitors

33
Q

Example of ion channel inhibitors

A

Influenza A

Adamantanamine derivatives
-M2 ion channel inhibitors (influenza A only)
-ex: amantadine, rimantadine
***does not allow proteins to uncoat

34
Q

What is a con of uncoating antiviral

A

rapid development of resistance

35
Q

What are examples of gene expression antivirals

A

Viral RNA polymerase inhibitors and endonuclease inhibitors

36
Q

What are the two types of gene expressionn antivirals

A

Viral RNA polymerase inhibitors (RNA viruses)—> (-) sense
— nucleoside and non nucleoside inhibitors (HCV, flu a and b, RSV, COVID)

⭐️ Endonuclase inhibitors (influenza)
-endonuclease necessary for 5’ cap snatching by influenza polymerase
-ex: baloxavir marboxil (Xofluza)
***steals caps from host and that it has this cap, it can function as mRNA and trick the virus into killing itself

37
Q

Example of Endonuclease inhibitor

A

baloxavir marboxil (Xofluza)

38
Q

What Are are replication antivirals?

A

viral DNA polymerase inhibitors

Reserve transcriptase inhibitors

39
Q

What are the two types of replication antivirals (DNA)? VERY HIGH YIELD

A

Acyclovir (ACV, Zovirax)

Ganciclovir (GCV)

40
Q

Explain acyclovir (ACV, Zovirax) HIGH YIELD

A

it is an guanosine analog

selectivity against HSV-1,2 and VZM

  1. Requires phosphorylation by VIRAL THYMIDINE KINASE (ACV-> ACV-MP)
  2. ACV-TP specifically inhibits viral DNA polymerase by competition with GTP
  3. CHAIN TERMINATION OF NASCENT DNA by incorporation of ACV-MP
    ***tricking virus to stop DNA replication
41
Q

Explain Ganciclovir (GCV) HIGH YIELD

A

Guanosine analog

Selectivity faint CMV and HSV

  1. Required phosphorylating by HSV TK OR CMV UL(& GENE (CMV does not encode a TK gene)
  2. GCV-TP specifically inhibits viral DNA polymerase by competition with GTP
  3. CHAIN TERMINATION NASCENT DNA by incorporation of GCV-MP

**tricking virus to stop replication

42
Q

viral resistance to acyclovir or fancicolivir

A

Mutation of TK gene (HSV)
-TK-neg mutants
-TK-low expression
-TK mutants (cannot phosphorylate ACV, GCV)

Mutation in the viral DNA polymerase
-can result in cross resistance to drugs that act directly on SNA polymerase

43
Q

List the 3 replication viral DNA polymerase inhibitors

A

Forscarnet (phophonoformic acid)
- organic analog of inorganic PYROPHOPHATE
- ACTS DIRECTLY ON VIRAL DNA POLYMERASE

Cidofovir (cytosine;HPMPC)
-NUCLEOSIDE ANALONG WITH PHOSPHONATE GROUP
-in vitro activity against HSV-1, HSV-2, VZV, CMV, EBV, adenovirus, HPC, human polyoma virus

Adfovir (PMEA), tenofovir (PMPA)
- ACUCLIC NUCLEOSIDE PHOSPHATE
- activity against retroviruses and HBV

44
Q

What is reverse transcriptase inhibitors

A

nucleoside analogs
- require phosphorylation
-ACTS AS CHAIN TERMINATOR OF NASCENT VIRAL DNA (HIGH YIELD)

non-Nucleosides inhibitors
- specifically bind NON-SUBSTRATE BINDING POCKEY OF HIV RT
-INHIBIT ENZYMATIC ACTIVTY

45
Q

What is an example of Budding/egress antiviral HIGH YIELD

A

Vital neuraminidase inhibitor: oseltamivir (tamiflu)

46
Q

What does oseltamivir (tamiflu) do?

A

Stops the neuraminidase from cleaving the receptor to allow the virus to be free, and it’s never released into circulation

47
Q

How can we target our own (cellular) proteins?

A

IMP Dehydrogenase Inhibitors (Ribavirin)

48
Q

How does IMP Dehydrogenase Inhibitors (Ribavirin) work?

A

GTP is limiting nucleoside in RNA synthesis. Ribavirin inhibits IMP dehydrogenase which is a required enzyme for GTP formation, we cannot have RNA synthesis

Microbiology (18 decks)

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