Anti-viral drugs

Question 1

Viral hepatitis

Answer 1

• tropism (liver hepatocytes)

- only chronic Hep B or Hep C infection requires treatment

Question 2

Hep C treatment

Answer 2

Ribavirin and peginterferon alfa
-ribavirin->nucleotide analogue preventing viral RNA synthesis

Boceprevir (protease inhibitor)
-most effective against Hep C genotype 1

Question 3

HIV life cycle

Answer 3

ATTACHMENT AND ENTRY
-viral membrane proteins interact with leukocyte membrane receptors
-viral capsid endocytosis
REPLICATION AND INTEGRATION
-reverse transcriptase enzyme converts viral RNA to DNA within cytoplasm
-DNA transported into nucleus and integrated into host DNA
ASSEMBLY AND RELEASE
-host cell machinery used to produce viral RNA and essential proteins
-virus assembled within cell=mature virion released

Question 4

Structure of HIV

Answer 4

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Question 5

HIV entry inhibitors (ATTACHMENT AND ENTRY)

Answer 5

Normal entry:

• HIV GP120 attaches to CD4 receptor
• GP120 also binds to either CCR5 or CXCR4
• GP41 penetrates host cell membrane and viral capsid enters

Drugs:

• Enfuvirtide=binds to HIV GP41 transmembrane protein
• Maraviroc=blocks CCR5 chemokine receptor

Question 6

HIV replication inhibitors (REPLICATION)

Answer 6

Normal replication:
-reverse transcriptase=viral single stranded RNA converted to double stranded DNA

Drugs:

• nucleoside reverse transcriptase inhibitor (eg: Zidovudine)=activated by 3 step phosphorylation process
• nucleotide reverse transcriptase inhibitor (eg: Tenofovir)=activated by fewer phosphorylation steps
• non-nucleoside reverse transcriptase inhibitor (eg: Efavirenz)=no phosphorylation required and not incorporated into viral DNA

Question 7

HIV integrase inhibitors (INTEGRATION)

Answer 7

Normal DNA integration:
-viral integrase inserts viral DNA into host DNA

Drugs: integrase inhibitors
-Raltegravir=licensed integrase inhibitor (first of 3 licensed)

Question 8

HIV protease inhibitors (ASSEMBLY AND RELEASE)

Answer 8

Normal assembly and release:

• Gag precursor= encodes all viral structural proteins
• HIV protease cleaves Gag precursor

Drugs: protease inhibitors

• Saquinavir= 1st generation protease inhibitor
• Low dose Ritonavir=reduces protease inhibitor metabolism and co-administered as booster to raise protease inhibitor concentrations

Question 9

Herpes simplex virus

Answer 9

Virology:
-double-stranded DNA
-surrounded by tegument and enclosed in lipid bilayer
Tropism:
-HSV-1=cold sores
-HSV-2=genital herpes
Treatment:
-nucleoside analogues (eg: Aciclovir)

Question 10

Influenza

Answer 10

Virology:
-multipartite single stranded RNA virus
-envelope protein neuraminidase activation->virus release
Tropism:
-nose, throat and bronchi
Treatment:
-Neuroaminidase inhibitor (eg: Oseltamivir)

Question 11

Hep B treatment

Answer 11

Tenofovir (nucleotide analogue)

-occasionally given with Peginterferon alfa

Question 12

HCV treatment goal

Answer 12

• cure virus
• done with combination of drugs
• the specific drugs used and treatment duration depends on HCV genotype, viral load, past treatment experience, degree of liver damage, ability to tolerate prescribed treatment, need for liver transplant etc)

Question 13

Direct acting antivirals

Answer 13

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