ID Quiz Pt2 - Herpes & Covid-19

What type of nucleic acid is carried by herpes virus

dsDNA

Does herpes virus use host polymerase or its own

its own viral DNA polymerase

Where is new herpes virus DNA replicated

In the host nucleus

Difference between nucleoside and nucleotide

-nucleoside: sugar base

-nucleotide: sugar base + phosphate

How many phosphates are needed on a nucleotide for DNA incorporation

3

difference between Acyclovir and Valacyclovir

Valacyclovir has an ester attachment which helps with absorption in the GI tract

Will acyclovir be activated in non-infected cells

no

MOA of Acyclovir

-enters the infected cell

-phosphorylated by viral kinase

-phosphorylated by host kinase X2

-INHIBITS VIRAL DNA POLYMERASE

-incorporated into viral DNA and acts as a chain terminator

Can acyclovir inhibit host DNA polymerase

yes

What does acyclovir compete with

deoxy-Guanosine-Tri-Phosphate (dGTP)

Acyclovir adverse effects

-Common: headache, nausea, diarrhea, rash

-Rare/serious: (when given by IV) nephro and neuro toxicity

Valacyclovir adverse effects

-headache nausea, diarrhea, rash

-more nephro and neurotoxicity (compared to acyclovir)

Acyclovir - valacyclovir resistance

-Impaired production of viral thymidine kinase

-altered TK substrate specificity

-altered viral DNA polymerase

Structure of Cidofovir

Acyclic nucleotide phosphate

Cidofovir MOA

-phosphorylated to active form by cellular enzymes

-Inhibits viral DNA synthesis

Cidofovir indication

Acyclovir resistant HSV infections

Cidofovir adverse effects

mutations in viral DNA polymerase (30% of patients after 3 months of treatment)

Foscarnet MOA

-inhibits HSV DNA polymerase

-binds to the pyrophosphate binding site

-inhibits cleavage of pyrophosphate from deoxynucleotide triphosphate

Foscarnet adverse effects

nephrotoxicity, hypocalcemia, CNS effects

Is docosanol a neucleotide

No - a lipid

Docosanol MOA

Blocks fusion between the cellular membrane and viral envelope

Docosanol application

Topical cream only effective in the early stages of a cold sore

What type of nucleic acid do corona viruses have

Positive RNA

Corona medications to reduce inflammation

Tocilizumab, Baricitinib

Corona medications that reduce viral replication

Remdesivir, Paxlovid

Baricitinib MOA

-Inhibits Janus Kinase

-Results in decreased transcription and translation of cytokines

-decreased immune response

Tocilizumab MOA

-Binds to IL-6 receptor

-results in suppression of IL-6 dependent signaling pathways

-reduces expression of inflammatory cytokines

-reduces immune response

Tocilizumab Black box warnings

-risk of infection, should be tested for TB

-Higher risk of certain cancers (lymphoma)

Baricitinib Black Box warnings

-heart attack or stroke

-cancer

-blood clots

-death

How is Remdesivir converted into active form

Phosphorylated into Remdesivir-P-P-P

Remdesivir MOA

Targets RNA dependent RNA polymerase of the virus

What two drugs are combined to make Paxlovid

nirmatrelvir, ritonavir

Paxlovid MOA

Inhibits the protease of the virus