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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
How do enveloped viruses leave the cell?
can bud at the plasm membrane or intracellular membranes IER, Golgi vesicles)
26
How do non enveloped viruses leave the cell
usually cause cell lysis
27
What are the two types of attactment- passive immunization antiviral
hyperimmune gamma globin monoclonal antibodies
28
What are examples of hyperimmune gamma globulin
CMV (cytogam) HAV, measles (BayGAM) HBV (Bayhep B, Nabi-HB) RSV (respigam)
29
What are examples of monoclonal antibodies
RSV (palivizumab, Synagis)L anti-F ZEBOV (ATO/MAF/ODE, inmazeb): anti-GP SARS CoV-2 (bebtelovimab, TIX/CIL: anti S (EUA)
30
What are the two types of entry antivirals
coreceptor antagonist fusion inhibitors
31
example the example given for coreceptor antagonist and fusion inhibitors
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
What is an example of uncoating in antiviral
ion channel inhibitors
33
Example of ion channel inhibitors
Influenza A Adamantanamine derivatives -M2 ion channel inhibitors (influenza A only) -ex: amantadine, rimantadine ***does not allow proteins to uncoat
34
What is a con of uncoating antiviral
rapid development of resistance
35
What are examples of gene expression antivirals
Viral RNA polymerase inhibitors and endonuclease inhibitors
36
What are the two types of gene expressionn antivirals
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
Example of Endonuclease inhibitor
baloxavir marboxil (Xofluza)
38
What Are are replication antivirals?
viral DNA polymerase inhibitors Reserve transcriptase inhibitors
39
What are the two types of replication antivirals (DNA)? VERY HIGH YIELD
Acyclovir (ACV, Zovirax) Ganciclovir (GCV)
40
Explain acyclovir (ACV, Zovirax) HIGH YIELD
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
Explain Ganciclovir (GCV) HIGH YIELD
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
viral resistance to acyclovir or fancicolivir
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
List the 3 replication viral DNA polymerase inhibitors
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
What is reverse transcriptase inhibitors
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
What is an example of Budding/egress antiviral HIGH YIELD
Vital neuraminidase inhibitor: oseltamivir (tamiflu)
46
What does oseltamivir (tamiflu) do?
Stops the neuraminidase from cleaving the receptor to allow the virus to be free, and it's never released into circulation
47
How can we target our own (cellular) proteins?
IMP Dehydrogenase Inhibitors (Ribavirin)
48
How does IMP Dehydrogenase Inhibitors (Ribavirin) work?
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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