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Discussion Starter · #1 ·
A chemotherapeutic agent classified as a guanosine derivative demonstrates significant antiviral activity against herpes simplexvirus type 1 herpes simplexvirus type 2, and varicella zoster virus. The same agent demonstrates weak antiviral activity against Epstein-Barr virus and cytomegaly virus. Which of the following best explains this difference in viral susceptibility to the drug?

A. Viral protease activity
B. DNA polymerase structure
C. Structural protein composition
D. Drug phosphorylation rate
E. Drug degradation rate
 

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Discussion Starter · #2 ·
Explanation:
The chemotherapeutic agent described here is most likely acyclovir, a guanosine analog. Once acyclovir enters the herpesvirus-infected host cell, it is converted to acyclovir monophosphate principally via a virally-encoded thymidine kinase (TK). This is the rate-limiting step in the activation of acyclovir. The acyclovir monophosphate is then phosphorated by cellular enzymes into the active triphosphate form, which impairs viral DNA polymerase-mediated replication of the virus.

Epstein-Barr virus (EBV) and cytomegalovirus (CMV) do not produce the same thymidine kinase that herpes simplex viruses (HSV) and varicella zoster virus (VZV) do. As a result EBV- or CMV-infected cells cannot easily convert acyclovir into its pharmacologically active triphosphate form. At very high intracellular concentrations some acyclovir appears to be activated by unidentified cellular phosphorylating enzymes, which may explain the partial susceptibility of EBV and CMV to higher acyclovir doses. In addition, the partial activity of acyclovir against CMV may be mediated by inhibited synthesis of a virus-specific polypeptide.
 

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Discussion Starter · #4 ·
So, to clarify, the answer is D, right? (I'm feeling not-so-smart today...) :eek:
Yes. You are smart all the time bro. I'm watching your activities here, you answer almost all question with reference posted by other members. I can see how much interest you are putting here to learn new things. I believe, you will be the one who can smash the board with 99+.
 
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