Anti-Influenza and Anti-Herpes Agents Med Chem Flashcards
Which of the following matching is incorrect?
A. HSV-1 / Cold Sore (Herpes Labialis)
B. HSV-2 / Genital Herpes
C. Varicella Zoster Virus (VZV) / Pneumonia
D. Cytomegalovirus (CMV) / pneumonia, blindness in immunocompromised patients
E. Epstein-Barr virus (EBV) / Infectious mononucleosis
C
DNA polymerase is responsible for viral replication by creating Viral DNA. In order for viral DNA to be synthesized you need ___ bonds in order to link the nucleotides together.
A. 1,6-phosphodiester
B. 3,5-phosphodiester
C. 3.5-phosphoester
E. Ionic
B
make sure you know that it is the 3’ OH that is making the nucleophilic attack on another nucleotide in order to link another nucleotide to the viral DNA chain.
All of the following medications are examples of Acyclic Nucleoside/Nucleotide medications EXCEPT:
A. Acyclovir, Valacyclovir
B. Ganciclovir/ Valgancyclovir
C. Penciclovir
D. Femciclovir
E. Cidofovir
F. Foscarnate
F
Foscarnate is a Non Nucleosidee DNA polymerase inhibitor
What Is the MOA of Acyclic Nucleoside/Nucleotide medications?
A. Inhibition of Viral DNA Polymerase
B. Inhibition of mammallian DNA polymerase only
C. Prevents the uncoating of the virus within the host cell
D. None of the above
A
Why are Acyclic nucleoside/nucleotide medications considered acyclic?
A. They do not contain cyclic bases
B. They do not contain cyclic sugars (glucose)
C. Their structure is linear and does not contain any cyclic structures
D. Their structure contains only a cyclic sugar but not a cyclic base.
B
If you compare the structures of the medications on the right their acyclic groups are incomplete sugars while on the left there is a normal nucleoside base with a cyclic sugar.
Which of the following Acyclic Nucleotide/Nucleoside medications is a Nucleotide?
A. Acyclovir
B. Valacyclovir
C. Famcyclovir
D. Cidofivir
E. Valgancyclovir
F. Gancyclovir
D. Cidofivir
Cidofivir is considered a nucleotide because it has a phosphate group in its structure along with a base. The others only have bases but no phosphate groups
Acyclovir is a ___ analog and competes with ___ in viral DNA.
A. Adenine, dATP
B. Thiamine, dTTP
C. Cytosine, dCTP
D. Guanine, dGTP
D
It is also known as Acyclo-G (guanine)
What makes Acyclovir selectively toxic?
A. The drug has higher uptake in normal mammalian cells
B. The drug has higher uptake in Herpes-infected cells.
C. The drug has high uptake regardless of cell infection
D. The drug has lower uptake in Herpes-infected cells.
B
What viral enzyme does Acyclovir need in order to be converted to Acyclovir Monophosphate?
A. katG
B. Pyrizanimidase
C. Thymidine Kinase
D. Does not require bacterial enzyme for initial phosphorylation
C
What are the Mechanisms of action of Acyclovir? (Select all)
A. Increases lysosome elimination of viral DNA
B. High affinity to herpes Thymidine kinase and uses it to convert to acyclovir monophosphate
C. AcTP (Acyclovir Tri-phosphate) will inhibit Viral DNA polymerase competitively
D. Can terminate the viral DNA chain, preventing it from growing and being completed. (Chain termination)
E. Can competitively inhibit Viral DNA Polymerase in either the AcMP, AcDP or AcTP form.
B, C, D
E is incorrect because Acyclovir has to be in the AcTP (tri phosphate) form in order to interact with Viral DNA polymerase. In other words it needs to undergo further phosphorylation from its monophosphate form before it can interact properly.
Look at slide 12
(Short Answer) What group in Acyclovir and any other Acyclic Nucloside/nucleotide medication is responsible for chain termination of Viral DNA and why?
The acyclic sugar group is responsible. Remember you need a 3’ OH in the cyclic structure in order to make nucleophilic attacks on phosphate groups of other nuclotides in order to link them together. In other words without these complete cyclic sugars you cannot form the 3’5’-phosphodiester bonds that are essential for Viral DNA replication.
When comparing the structures of Acyclovir and Valacyclovir: Valacyclovir has a ___ functional group. This makes it a ____.
A. Valine, Prodrug
B. Valine, Active drug
C. Isoleucine, Prodrug
D. Propylene, Prodrug
A
The valine group makes it a prodrug and allows it to have better oral absorption. (70%)
Remember Valacyclovir=Valine.
I think she also wants us to know the metabolite at the end. (slide 13)
When a patient has anuria the half-life of valacyclovir becomes ___ and the dose should be ____.
A. 3 hours, Reduced
B. 20 hours, Increased
C. 20 hours, Reduced
D. 3 hours, increased
C
Valacyclovir unddergoes renal elimination and if the patient has anuria they will not be able to excrete the medicaiton from their body as easily.
Acyclovir and Valacyclovir are meant to treat all of the folowing EXCEPT:
A. HSV-1
B. HSV-2
C. VZV infections
D. CMC infections
D
Remember Valacyclovir has the letter “V” in it so it can treat viruses that contain the letter V. EXCEPT EBV
HSV-1
HSV-2
VZV
What is the mechanism of viral resistance to Valacyclovir and Acyclovir?
A. Reduction of virus encoded Thymadine Kinase
B. Reduction of virus encoded katG
C. Reduction of virus encoded Pyrazinamidase
D. No resistance mechanism against valacyclovir or acyclovir
A
Remember Valacyclovir and Acyclovir require Viral Thymadine Kinase in order for the initial phosphorylation of the medication to happen (Acyclovir-monophosphate). Without that step it cant become phosphorylated to its Tri-phosphate form (AcTP) and won’t be able to block Viral DNA Polymerase.
katG activates Isoniazid
Pyrazinamidase activates Pyrazinamdie
When comparing the structures of Famciclovir and Penciclovir, which of the following statments is true? (Select All)
A. The ester groups circled on Famciclovir increasesthe oral absorption of the medication.
B. The free OH groups on Penciclovir allow it to be well tolerated and absorbed orally.
C. Penciclovir is a derivative of Famciclovir
D. Penciclovir is topical formulations such as creams for Herpes Labalis
A, C, D
B is wrong because the free OH groups decrease the oral absoprtion of penciclovir
Due to the free OH groups in penciclovir it is better used topically for HSV infections but only on the face and lips.
When comparing the structures of Ganciclovir and Valganciclovir what is the main difference?
A. Guanine group present on Ganciclovir
B. Valine goup present on Valganciclovir
C. Valine group present on the Ganciclovir
D. Guanine group present on the Valganciclovir
B
The difference between Ganciclovir and Valganciclovir is the same as Acyclovir and Valacyclovir
Valganciclovir-Valine
T/F The valine group in valcanciclovir allows the drug to be used as a topical gel/jelly while the free OH groups in ganciclovir allow the drug to be given orally.
F
Cidofovir is different from the other Acyclic Nucleoside medications: (Select all)
A. It is a Nucloside analog and not a nuclotide analog
B. It is a Nuclotide analog and not a nucloside analog
C. It conains an incomplete acyclic sugar and the others have cyclic sugar groups
D. It already has a phosphate group in its structure
E. It does not require a viral enzyme to be converted to its inital monophosphate form
B, D, E
Remeber Cidofovir= Phosphate
Because it has this phosphate group it is considered a nuclotide analog and not a nucleoside analog
Since it already has its first phosphate group it is already in it’s monophosphate form and does not require a viral enzyme for initial phosphorylation.
Based on the structure of Foscarnate, we can conclude that is is most likely administered:
A. Orally
B. IV
C. Topically
D. Rectally
B
When the virus is ready to be released from the infected host cell (viral release) what receptors have to be cleaved in order to release the virus so it can infect other cells?
A. Sialic acid receptors
B. CD4 receptors
C. CXCR4 receptors
D. CCR5 receptors
A
The receptors containing Sialic acid need to be broken in order for the virus to be released so it can continue infecting other host cells.
What is the MOA of Zanamivir and Oseltamivir?
A. Inhibition of viral Neuraminidase
B. Inhibition of viral DNA polymerase
C. Direct lysing of viral DNA
D. None of the above
A
The hemagglutinin portion of the influenza virus is attached to the sialic acid receptors on a host cell. When the virus is ready to be released from the host cell neuraminidase cleaves the receptor-hemagglutinin linkage and releases the virus from the host cell so it can spread to other cells. If we use these medications to block neuraminidase the virus can’t be released from the cell and it will prevent the spread of the infectious virus to other bodily cells.
What do the medications Zanamivir and Oseltamivir resemble in order to make them effective at binding to neuraminidase and blocking it?
A. Sialic Acid from host cell
B. Sialic Acid from viral cell
C. The transition state of Sialic Acid
D. Neuraminidase
C. Transition state of sialic acid
She wants us to know that the medications zanamivir and oseltamivir mimic the transition state of sialic acid. This picture shows the structural similarity between the transition state and the structure of the medications.
When looking at the structure of Zanamivir, the circled ___ functional group allows the medication to be taken by ___.
A. Urea, mouth
B. Guanidino, Oral inhalation
C. Guanidino, topical preparation
D. Urea, Oral inhalation
B
The circled groups in Oseltamivir allow the medication to be taken ____
A. IV
B. Intranasally
C. Oral inhalation
D. Orally
D
The group on the upper left is a carbon chain that is lipophilic and promotes hydrophobic interactions (helps in the binding pocket of neuraminidase). The group circled on the right is an ester group that was added onto the carboxylic acid. This makes the drug highly lipophilic and able to be taken orally.
Look at slide 27 for diagram of enhanced interactions between the drugs and neuraminidase
The picture provided shows two different reactions that Oseltamivir can undergo. ___ reaction is needed to make the active metabolite and the ___ reaction is needed to make the inactive metabolite.
A. Ester hydrolysis, W-oxidation
B. Reduction, W-oxidation
C. Ester hydrolysis, Reduction
D. Reduction, Ester hydrolysis
A
w-oxidation means omega oxidation. Remember the omega carbon is the last carbon so this is an omega carbon oxidation. It can happen at any of the two points circled since they are both omega carbons. It is then further oxidized to make a carboxylic acid.
For resistance to zanamivir and oseltamivir look up slide 30. Picture is unclear and making a question on it can be confusing.
