Microbiology: Mechanisms of resistance

Question 1

Where can antiviral drugs target?

Answer 1

Drugs which target viral proteins e.g. inhibition of virus replicative enzymes
Drugs which target host proteins e.g. blocking receptors
Drugs which enhance host defenses e.g. interferons

Question 2

Why is selectivity important in antiviral therapy?

Answer 2

Selectivity = difference between the dose of drug which inhibits the viral protein versus any similar cellular protein

Question 3

How can antivirals inhibit virus attachment and entry?

Answer 3

May target viral proteins
– e.g. drug Enfuvirtide binds to HIV envelope

May target host cell receptors
– e.g. drugs which block HIV co-receptors (CCR5)

Question 4

How can antivirals inhibit viral uncoating?

Answer 4

Example: Influenza A

The mechanism of amantadine’s antiviral activity involves interference with the viral protein, M2, a proton channel.

Question 5

How can antivirals inhibit genome replication?

Answer 5

Inhibition of viral polymerase
Nucleot(s)ide analogues – incorporated into viral genome and stops elongation
Antiretroviral drug – Bind near catalytic site of RT

Question 6

How can antivirals inhibit Virus Assembly?

Answer 6

Protease inhibitors
Where viral proteins are produced as polyproteins and require cleavage by a protease this is a good drug target
Used for HIV, hepatitis C in man

Question 7

How can antivirals inhibit virus release?

Answer 7

Neuraminidase inhibitors

Prevent release of influenza virus from cells

Question 8

Is resistance more of a problem in RNA or DNA viruses?

Answer 8

More of a problem in RNA viruses with inherently higher mutation rate

Question 9

How do we treat feline retroviruses FeLV and FIV

Answer 9

Feline interferon omega (Virbagen Omega; Virbac)

Nucleotide analogues: zidovudine has been used – but renal toxicity