Antivirals!

Question 1

6 stages of viral replication

Answer 1

1) attachment, 2) engulfment, 3) uncoating, 4) replication, 5) assembly, 6) release

Question 2

viruses that cause chronic disease: reactivation of acute, chronic and neoplasia

Answer 2

reactivation of acute: HSV, VZV

chronic disease - HBV, HCV

neoplasia- EBV, HPV, HHV-8, HBV, HCV

Question 3

viruses that cause latent disease (subclinical)

Answer 3

CMV, EBV, HIV, SSPE, PML

Question 4

Antivirals for herpes viruses: 4

Answer 4

ACYCLOVIR - hsv, ebv, vzv
GANCYCLOVIR - cmv
CIDOFIVIR- cmv, adenovirus, poxvirus
FOSCARNET- cmv, hsv

Question 5

Mechanism of acyclovir

Answer 5

acyclovir prodrug is phosphorylated by THYMIDINE KINASE to get acyclovir triphosphate, which competitively inhibits deoxyguanosine triphosphate (and inhibits viral DNA polymerase.)

Question 6

3 mechanisms of acyclovir resistance

Answer 6

decreased thymidine kinase, decreased affinity of thymidine kinase for drug, decreased absorption

Question 7

Influenza antivirals - name the 2 big classes

Answer 7

1)neuraminidase inhibitors, 2) m2 ion channel blockers (historic interest only) - examples amantidine and rimantidine

Question 8

talk about neuraminidase inhibitors

Answer 8

2 examples: zanamivir + oseltamivir

mechanism: inhibit neuraminidase, which cleaves sialic acid from virions (prevents clumping, and allows virions to leave cell)

Question 9

HCV antivirals - direct acting and nonspecific

Answer 9

direct acting: protease inhibitors - linear + macrocyclinc (low genetic barrier to resistance).

nonspecific:
INTERFERONS - alpha, beta and gamma. Increase host resistance to viral infection (increase # inhibitory proteins for RNA synthesis, enzymes to cleave viral DNA, inhibit viral mRNA, alter host PM.

RIBAVIRIN - purine analog. Thoguht to alter nucleoside pools and inhibit RNA synthesis. Causes lethal mutagenesis of some RNA viruses. Sindbis + HCV are resistant

Question 10

HIV Antiretrovirals - all target reverse transcriptase

Answer 10

1) CCR5 receptor inhibitors - prevent gp120 from binding to CCR5 cytokine R.
2) fusion inhibitors - prevent gp41 from binding to host cel (Enfuvirtide)
3) NRTI/NNRTIs - bind to RT at NNRTI/NRTI binding pocket and displace active site of RT (low genetic barrier to resistance)
4) integrase inhibitors - prevent HIV from integrating its genome into host cell
5) protease inhibitors - prevent HIV virions from being released (low genetic barrier to resistance)