Anti-Influenza and Anti-Herpes Agents Med Chem

Question 1

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

Answer 1

C

Question 2

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

Answer 2

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.

Question 3

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

Answer 3

F

Foscarnate is a Non Nucleosidee DNA polymerase inhibitor

Question 4

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

Answer 4

A

Question 5

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.

Answer 5

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.

Question 6

Which of the following Acyclic Nucleotide/Nucleoside medications is a Nucleotide?

A. Acyclovir

B. Valacyclovir

C. Famcyclovir

D. Cidofivir

E. Valgancyclovir

F. Gancyclovir

Answer 6

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

Question 7

Acyclovir is a ___ analog and competes with ___ in viral DNA.

A. Adenine, dATP

B. Thiamine, dTTP

C. Cytosine, dCTP

D. Guanine, dGTP

Answer 7

D

It is also known as Acyclo-G (guanine)

Question 8

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.

Answer 8

B

Question 9

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

Answer 9

C

Question 10

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.

Answer 10

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

Question 11

(Short Answer) What group in Acyclovir and any other Acyclic Nucloside/nucleotide medication is responsible for chain termination of Viral DNA and why?

Answer 11

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.

Question 12

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

Answer 12

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)

Question 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

Answer 13

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.

Question 14

Acyclovir and Valacyclovir are meant to treat all of the folowing EXCEPT:

A. HSV-1

B. HSV-2

C. VZV infections

D. CMC infections

Answer 14

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

Question 15

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

Answer 15

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

Question 16

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

Answer 16

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.

Question 17

Famciclovir and Penciclovir are used in the treatment of ___ and ___

A. HSV, EBV

B. HSV, CMC

C. HSV, VZV

D. HSV, M.tuberculosis

Answer 17

C. HSV, VCV

Question 18

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

Answer 18

B

The difference between Ganciclovir and Valganciclovir is the same as Acyclovir and Valacyclovir

Valganciclovir-Valine

Question 19

What is the mechanism of action of Ganciclovir and Valganciclovir?

A. Inhibition of Viral DNA polymerase

B. Destruction of viral cell wall

C. Direct lysing of viral DNA

D. None of the above

Answer 19

A

Same MOA as Acyclovir and Valacyclovir.

Question 20

If the MOA of Gancyclovir and Valgancyclovir is identical to that of Acyclovir and Valacyclovir, what viral enzyme is needed to convert Ganciclovir and Valganciclovir to their initial mon-phosphate form?

A. katG

B. Pyraziamidase

C. Thymadine Kinase

D. UL97 Gene-encoded Phosphotransferase

Answer 20

D

The MOAs are identical between the pairs Gancilcovir/Valganciclovir and Acyclovir/Valacylcovir. Where they are different is in what phosphotransferase they use to be converted to their monophosphate forms.

Also, UL97 gene encoded phosphotransferase is only seen in CMV so in other words Ganciclovir and Valganciclovir are both used in the treatment of CMV infections.

Question 21

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.

Answer 21

F

Question 22

What major adverse effect of Ganciclovir and Valganciclovir make it unusable in pregnant patients

A. Nausea

B. Vommiting

C. Carcinogenic/ tetratogenic

D. CNS toxicity

Answer 22

C

Question 23

What is the mecahnism of viral resistance to Ganciclovir and Valganciclovir?

A. Reduction of virus-encoded thymadine kinase

B. Mutation in viral phosphotransferase UL97

C. Mutation in katG bacterial enzyme

D. No known resistance to Ganciclovir or Valganciclovir

Answer 23

B

There is a gernal theme of viral resistance to these medications. It happens by either reducing or mutating the phosphotransferases that are required to convert the medications to their initial monophosphate forms.

Question 24

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

Answer 24

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.

Question 25

In what situations is Cidofovir used? A. Used to treat acyclovir-resistant HSV B. Used to treat Ganciclovir resistant CMV infections C. Treatment of CMV retinitis in HIV patients only. D. All of the above

Answer 25

D if viruses become resistant to ganciclovir and acyclovir then that means they either mutate or reduce expression of the viral phosphotransferases that are needed for the drug. However, Cifofovir does not require a viral enzme for initial its phosphorylation because it already has a phorphorus group on it. So it makes sense that we would use this medication when resistance occurs to the other agents.

Question 26

T/F The non-nucloside inhibitor of DNA polymerase Foscarnate is used to treat CMV retinitis and acyclovir-resistant HSV and VZV infections.

Answer 26

T

Question 27

Based on the structure of Foscarnate, we can conclude that is is most likely administered: A. Orally B. IV C. Topically D. Rectally

Answer 27

B

Question 28

What is the mecahnism of action of the non-nucleoside medication Foscarnate? A. Inhibition of Viral DNA Polymerase B. Direct lysing of viral DNA C. Viral Cell wall destruction D. None of the above

Answer 28

A Same general MOA of NRTIs but the difference is that this medcation is NOT a nucloside or a nuclotide because its structure lacks a base and/or phosphate groups.

Question 29

The influenza virus can cause increased chances of developing Reye's syndrome in children and adolescents. As a result children should not use ___ in management of influenza symptoms. A. Ibuprofen B. Naproxen C. Acetaminophen D. Aspirin

Answer 29

D

Question 30

Which of these Anti-Influenza agents inhibits viral uncoating? (Select all) A. Armantadine B. Zanamivir C. Oseltamivir D. Rimantadine E. Acyclovir

Answer 30

A, D Remember: the medcations ending in **"tadine****"**inhibit viral uncoating. Aman**tadine**Riman**tadine**.

Question 31

Which of these Anti-influenza Agents inhibits viral release? (Select All) A. Acyclovir B. Zanamivir C. Amantadine D. Rimantadine E. Oseltamivir

Answer 31

B, E

Question 32

Why are Anti-influenza agents amantadine and ramantidine medications no longer recommended for treatment or prophylaxis of influenza infections? A. Carcinogenic to most patients B. Adverse effects far outweigh the benefits C. Widespread viral resistance to these types of medications D. Extremely costly to hospital and patients.

Answer 32

C

Question 33

When using the Anti-influenza Agents Zanamivir and Oseltamivir, when is treatment the most effective? A. Within 48 hours of onset of symptoms B. Within 72 hours of onset of symptoms C. At least 48 hours after the onset of symptoms D. At least 72 hours after the onset of symptoms

Answer 33

A The reason why these agents are used is because they inhibit viral release from infected cells (detachment). If they are not used within 48 hours then the medication is useless because the virus has already been released from the infected cells and is now in the replication step.

Question 34

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

Answer 34

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.

Question 35

What viral enzyme is responsible for breaking the sialic bonds between the host cell and the virus, leading to viral release? A. Viral Peptidase B. Viral Neuraminidase C. Viral Protease D. Viral Lipase

Answer 35

B

Question 36

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

Answer 36

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.

Question 37

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

Answer 37

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.

Question 38

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

Answer 38

B

Question 39

The circled groups in Oseltamivir allow the medication to be taken \_\_\_\_ A. IV B. Intranasally C. Oral inhalation D. Orally

Answer 39

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**

Question 40

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

Answer 40

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.**