Antiviral Drugs

Question 0

Types of antivirals

Answer 0

Nucleoside analogs
Non-nucleosides
Protease inhibitors
Entry inhibitors

Question 1

Types of treatments for viruses

Answer 1

Virucidal (detergents, cryotherapy)
Immunomodulatory (interferon, help host fight)
Antiviral

Question 2

How do antiviral drugs work?

Answer 2

Target essential virus functions
Target host cell defenses (intrinsic immunity)
Activate immune response

Question 3

Antiviral issues

Answer 3

Specificity: broad spectrum drugs are rare because most target functions of only one virus due to the diversity of viruses

Cytotoxicity: “off target” effects can harm cells (a-interferon), “on target” drugs directed at viral enzymes can be defeated by resistance mutations

Duration of antiviral effects: most drugs are reversible

Question 4

Resistance to antivirals

Answer 4

Resistance mutations often present in patient even before drug treatment, treatment selects for resistant virus strains

Factors factoring emergence of resistant variants: High rate of virus replication, high mutation rate (RNA), high selective drug pressure (long term use, multiple treatments), immunosuppressed host can’t clear virus-infected cells

Question 5

Counter resistance to antivirals

Answer 5

Alleviate immunosuppressive (lower dose of anti-T cell drugs, combine drugs with different targets, target host functions

Question 6

Treatments for Herpes viruses HSV-1, HSV-2 and VSV

Answer 6

DNA viruses
Neonates, frequent occurrences, complications, zoster should be treated
Acyclovir: nucleoside analog of guanosine (only recognized by viral DNA polymerase, when incorporated it is a viral DNA chain terminator that stops replication)

Question 7

Treatment for CMV

Answer 7

DNA virus

Ganciclovir: nucleoside analog of guanosine, similar to acyclovir, highly toxic because also recognized by host DNA polymerase

Question 8

Broad spectrum treatments for DNA viruses

Answer 8

Foscarnet: inhibits viral DNA polymerase, effective against all herpesviruses, toxic to kidneys

Cidofovir: nucleoside analog of cytosine, effective against DNA viruses, toxic to kidneys

Question 9

Treatments for hepatitis B virus

Answer 9

Treated with drugs designed for HCV and HIV (has reverse transcription)

Pegylated interferon alpha, entecavir, tenofovir disoproxil fumarate

Question 10

Treatment for influenza

Answer 10

RNA viruse

Zanamivir and Oseltamivir: both are sialic acid analogs that inhibit viral neuraminidase (sialidase), prevents spread via release of virions from cell membrane

Question 11

Broad spectrum treatment for RNA viruses

Answer 11

Ribavirin: nucleoside analog of guanosine, targets RDRP enzyme for viral replication

Question 12

Treatments for hepatitis C virus

Answer 12

Combination therapy Peg-interferon-a with ribavirin

Has bad side effects

Question 13

Treatments for HIV

Answer 13

AZT: first drug for HIV, nucleoside analog of thymidine

Classes of anti-HIV drugs:
Entry inhibitor (Maraviroc)
Nucleoside RT inhibitor (Tenofovir)
Non-nucleoside RT inhibitor (Efavirenz)
Integrate inhibitor (Raltegravir)
Protease inhibitor (Darunavir)

Stribild is a one pill, 4 drug combination with Elvitegravir (integrase inhibitor), Cobicistat (inhibits liver enzyme that breaks down drugs in liver, boosts potency of Elvitegravir), Emtricitabine (RT inhibitor), Tenofovir disoproxil fumarate (RT inhibitor)