Antivirals Slackers Facts by Mike Ori

Disclaimer The information represents my understanding only so errors and omissions are probably rampant. It has not been vetted or reviewed by faculty. The source is our class notes. The document can mostly be used forward and backward. I tried to mark questionable stuff with (?). If you want it to look pretty, steal some crayons and go to town. Finally… If you’re a gunner, buck up and do your own work.

At what steps in the virus replication process can antivirals be effective

1.Attachment 2.Penetration 3.Uncoating 4.Replication 5.Assembly 6.Release

What is the mechanism of action and target virus for amantadine and rimantadine

Interfere with matrix proteins of the influenza virus to prevent uncoating.

Describe oseltamivir’s mechanism and target virus

Oseltamivir interferes with influanza A and B neuraminidase action thus preventing attachment (?) and release

Describe the mechanism of nucleoside/nucleotide analogs

Interfere with RNA and DNA synthesis by introducing chain terminating nucleotides into the nascent chain.

Describe the action of acyclovir

A chain terminating nucleoside analog that is efficiently monophosphorylated by herpes virus thymidine kinase and then triphosphorylated by cellular kinases. Thus its action is limited to cells infected with herpes virus.

Which herpes virus is acyclovir ineffective against and why.

Ineffective against CMV because it is not efficiently mono-phosphorylated by CMV’s thymidine kinase

How does acyclovir destroy cells with latent virus

It does not. Viral thymidine kinase must be expressed.

What is the alternative to acyclovir for CMV infection?

Gancyclovir is efficiently phosphorylated by CMV’s kinase.

What is the class and mechanism of ribavirin

A general nucleic acid synthesis inhibitor that prevents guanosine 5’-phosphate synthesis through unknown mechanisms.

Inhibition of which proteins would prevent the attachment of HIV

GP41 -> CD4 GP120 -> CCR5

Define the action of nucleoside reverse transcriptase inhibitors

A chain terminating nucleotide analog that interferes with HIV reverse transcriptase.

What is the prototypical NRTI

Azidothymidine (AZT)

Describe the mechanism of action of non- nucleoside reverse transcriptase inhibitors

Allosterically interferes with the action of HIV reverse transciptase.

Describe the mechanism of action of integrase inhibitors

Interferes with the function of HIV integrase to prevent the insertion of HIV DNA into the host chromosomes.

Describe the mechanism of action of protease inhibitors

Competitively (?) inhibit HIV proteases that cleave gag ployproteins to their mature forms.