Antivirals

Question 1

Zanamivir, oseltamivir

Answer 1

Inhibit influenza neuramindase leading to decreased release of progeny virus

Treatment and prevention for both influenza A and B

Question 2

Ribavirin

Answer 2

Inhibits synthesis of guanine nucleotides by competitively inhibiting inosine monophosphate dehydrogenase

Treatment for RSV, chronic hep C

Cause hemolytic anemia

Severe teratogen

Question 3

Acyclovir, famciclovir, valacyclovir

Answer 3

Monophosphorylated by HSV/VZV thymidine kinase and not phosphorlyated in uninfected cells –> fewer side effects

Guanosine analog, triphosphate formed inhibits viral DNA polymerase by chain termination

Used for HSV and VZV, weak activity against EBV, no activity against CMV

Cause obstructive crystalline nephropathy and acute renal failure if not adequately hydrated

Resistance caused by mutated viral thymidine kinase

Question 4

Ganciclovir

Answer 4

Monophosphate formed by CMV viral kinase. Guanosine analog, triphosphate formed inhibits viral DNA polymerase

Treatment for CMV especially in immunocompromised patients

Cause leukopenia, neutropenia, thrombocytopenia, and renal toxicity

Resistance caused by mutated CMV DNA polymerase or lack of viral kinase

Question 5

Foscarnet

Answer 5

Viral DNA polyermase inhibitor that binds to the pyrophosphate-binding site of the enzyme

Does not require activation by viral kinase

Treatment for CMV retinitis when gancyclovir fails
Acyclovir resistant HSV

Causes nephrotoxicity

Resistance caused by mutated DNA polymerase

Question 6

Cidofovir

Answer 6

Inhibit viral DNA polyemerase. Does not require activation by viral kinase

Treatment for CMV retinitis, acyclovir resistant HSV

Causes nephrotoxicity

Question 7

HIV therapy

Answer 7

HARRT: initiated when patients presents with AIDS-defining illness or CD4 count below 500, or high viral loads

Regimen consists of 3 drugs:
2 nucleoside reverse transcriptase inhibitors NRTI
+
1 non-nucleoside reverse transcriptase inhibitor NNRTI
OR 1 protease inhibitor
OR 1 integrase inhibitor

Question 8

Protease inhibitor

Answer 8

Atazanavir
Lopinavir
Navir tease a protease

Assembly of visions depends on HIV-1 protease (pol gene), which cleaves the polypeptide products of HIV mRNA into their functional parts. Thus protease inhibitors prevent maturation of new viruses

Cause hyperglycemia, GI intolerance, nephropathy

Question 9

NRTIs

Answer 9

Tenofovir (nucleotide, does not need to be phosphorylated)
Zidovudine (and others are nucleosides, need phosphorylation), used for general prophylaxis and during pregnancy

Competitively inhibit nucleotide binding to reverse transcriptase and terminate the DNA chain (nucleotide here lacks 3’ OH group)

Cause bone marrow suppression, peripheral neuropathy, anemia

Question 10

NNRTIs

Answer 10

Nevirapine, delaviridine

Bind to reverse transcriptase at site different from NRTIs
Do not require phosphorylation to be active or compete w/ nucleotides

Cause rash, hepatotoxicity

Question 11

Integrase inhibitor

Answer 11

Raltegravir

Inhibit HIV genome integration into host cell chromosome by reversibly inhibiting HIV integrase

Cause hypercholesterolemia

Question 12

Enfuvirtide

Answer 12

HIV fusion inhibitor

Binds gp41, inhibiting viral entry

Cause skin reaction at injection site

Question 13

Maraviroc

Answer 13

HIV fusion inhibitor

Binds CCR5 on surface of T cells/monocytes to prevent interaction w/ gp120

Question 14

Inteferons

Answer 14

Glycoproteins normally synthesized by virus-infected cells
Exhibit wide range of antiviral and antitumoral properties

IFNalpha: chronic hep B and C, Kaposi, renal cell carcinoma, malignant melanoma

IFNbeta: mutliple scerlosis

IFNgamma: chronic granulomatous disease

Cause neutropenia and myopathy