21 Virus: Antivirals and Vaccines

Question 1

Antivirals(2)

Answer 1

virostatic, have only modest effect when individual is already infected, but can stop infection once it has started

Question 2

Common Pitt-Falls for antivirals

Answer 2

Agent that reduces virus virleunce or replication leads to selection pressure for resistant viruses, vaccine escape mutants and increased virulence

Virus are obligate intracellular, host virus relationship intervention has risk for host (side effects)

Question 3

Why are there so few antiviral drugs?

Answer 3

Side effects that are unacceptbale

Medically important viruses are dangerous: cant be tested in modell system or cant be propagated (no grow in lab, no animal modell, dangerous)

Partial inhibition no option (resistancies)

many disease have short duration, therapy start would be too late, prophylaxis safety issues

Question 4

Broad targets

Answer 4

Interferon (Hepatitis)

Nucleoside analoug (HIV)

Question 5

Avoiding resistances
HIV
Influenza

Answer 5

HIV
HAART
3-4 drugs with at least 2 different targets, probability of resistance is product of individual resistances

Influenza
Amantidine (M2 ioin channel) resistancy often

Question 6

Nucleoside Inhibitors
example
virus
mechanism

Answer 6

example
Acyclovir, nuclei acid analogue prodrug that acts as an antimetabolite to stop DNA synthesis, side effects

Virus
Herpes

Question 7

Pro drug advantages

Answer 7

improve membrane permeability, solubility and absorption

alter metabolism, toxicity and elimination

Question 8

Osletamivir / Zanamivir

Answer 8

pro drug that binds sialic acid to inhibit neuramnidase for viral release and spreading

active form would be Zanamivir

Question 9

HCV antivirals
name
examples
costs

Answer 9

past: Ribavirin, Interferon

Direct acting antivirals
Hepatitis C

Protease (previr)
NS5A (asvir)
non nucleoside and nucleoside NS5B (buvir)

very expensive therapy (>100k)

Question 10

Drug discovery

Answer 10

Target identification
Hit identification
Hit to lead
developing leads
developing drug
clinical trials 1-4

Question 11

Example of passive immunization

Answer 11

Rabies Immune globulin for short term protection

Question 12

Requirements for effective vaccine

Answer 12

cheap (less than 1$)

Genetic stability, storage, delivery

Safety

protective immunity for long time

Question 13

Different type of vaccine, short description and example

Answer 13

Live attenuated virus
culture of pathogenic virus in other species cells, so mutation lead to lower virulence in humans

Induces mild or no disease

e.g. OPV Sabin against Polio but reversion was possible

Inactivation
by chemicals like formalin to eliminate infectivity but not antigenicity, more doses needed to build immune response
+ adjuvant
e.g. IPV Salk against Polio prevents CNS infection

Fractionation
subunits, often capsid or membrane protein
can be expressed in bacterial, insect culture using the plasmid for the protein

Question 14

Clinical trials and reason

Answer 14

1: Safety

2: Expanded Safety

3: Safety and Efficacy

Question 15

Antivirals, virus and target

Answer 15

DNA Polyermase
Herpesvirus: ciclovir

Viral uncoating
Influenza: Amantidine

RT
HIV: Zidovudine

Protease
HIV: Lopinavir

Neuraminidase
Oseltamivir, Zanamivir

Inosine monosphospate dehydrogenase
RSV: Ribavirin

Question 16

Different kind of vaccines

Answer 16