Antivirals

Question 1

Acyclovir

Answer 1

HSV drug
* Guanosine analogue
* Viral thymidine kinase adds P-O to it instead of guanine -> lacks a 3’ OH so cannot accept a base
* Less active against VZV and more against CMV, EBV, HHV-6
Resistance:
- loss or mutation in thymidine kinase
- mutation in DNA pol (clinically relevant)

Question 2

Ganciclovir

Answer 2

Mainly CMV drug used in immunocompromised
* Guanosine analog that targets a protein kinase UL97
-> termination of chain elongation
* binds preferentially to viral DNA pol but can bind cellular
* has activity in Herpes family viruses
Resistance:
-Mutations in UL97
-mutations in DNA pol

Question 3

Cidofovir

Answer 3

Used in HSV (acyclovir resistance) and CMV (ganciclovir resistance) - CMV retinitis in AIDs patients
* activity against all herpes viruses
* Cytidine analogue
* cellular enzymes add
* toxicity in kidney occasionally
Resistance from DNA pol mutations

Question 4

Foscarnet

Answer 4

Pyrophosphate analogue, prevents cleavage of pyrophosphate from dNTPs stopping DNA synthesis
* mainly used in ganciclovir- resistant CMV in AIDS
* Also HSV or VZV that is acyclovir resistant

Question 5

HBV nucleotide analogs

Answer 5

Tenofovir - adenine analog
Entecavir - deoxyguanosine analog

Question 6

Peginterferon-α2a for HBV

Answer 6

Activates type 1 Interferon in hepatocyes that;
limit protein synthesis and induce viral mutagenesis
* Increases MHC-1 expression on infected cells

Question 7

Ribavirin (HCV)

Answer 7

Older therapy; Guanosine analog that depletes pools of guanosine triphosphate

Question 8

Protease inhibitors in HCV

Answer 8

NS3/NS4A protease inhibitor
NS5a inhibitor more potent and less likely for mutants

Question 9

Adamantanes

Answer 9

Influenza drug
* Inhibits M2 - intereres with uncoating
only works for influenza A

Question 10

Neuraminidase inhibitors

Answer 10

Oseltamivir (Tamiflu)
*Prevents entry back inhibiting neuraminidase
* Neuraminidase cleaves sialic acid receptor allowing entry

Question 11

Baloxavir marboxil

Answer 11

Influenza
Inhibits PA subunit of RNA polymerase
- Eliminates use of host mRNA caps for viral mRNA synthesis

Question 12

Ribavirin for RSV

Answer 12

Guanosine analog that induces excess number of mutations
* Also depletes GTP pool
* Used for immunocompromised patients
* active against DNA and RNA viruses

Question 13

Palivizumad

Answer 13

RSV prophylaxis
* Monoclonal antibody - epitope of F protein

Question 14

Paxlovid (ritonavir-boosted nirmatrelvir)

Answer 14

Nirmatrelvir = protease inhibitor
Ritonavir = protease inhibitor & cytochrome P450 (CYP) 3A4 inhibitor

Question 15

Remdesivir

Answer 15

adenosine analog; stalls RdRp resulting in chain termination

Question 16

Molnupiavir

Answer 16

Prodrug (N4-hydroxycytidine, NHC) is metabolized in cells to yield a triphosphate form (NHC-TP)
- Competes with CTP or UTP

Question 17

Anti-SARS-CoV-2 monoclonal antibodies

Answer 17

Bebtelovimab:neutralizing human mAb binds to the spike protein of SARS-CoV-2
Tixagevimab plus cilgavimab:human mAbs bind to nonoverlapping epitopes of the spike protein

Question 18

Antiretroviral Entry inhibitors

Answer 18

Temsavir, binds to HIV gp120 and prevents normal attachment of the host CD4
Ibalizumab - prevents gp120 conformational change for binding

Question 19

CCR5 inhibitor – Maraviroc

Answer 19

Binds to host CCR5 - preventing HIV binding
- not used for initial therapy
- need to check for affinity to CXCR4

Question 20

Fusion inhibitor – Enfuvirtide

Answer 20

Blocks gp41 conformational change by preventing interaction between HR1 and HR2 regions
- not used for initial therapy

Question 21

Nucleoside reverse transcriptase inhibitors (NRTIs)

Answer 21

Nucleoside analogues – require phosphorylation for activation
-“Backbone” of ART
Typical therapy involves 2 NRTIs in combination with a 3rd agent from a different class of anti-retrovirals

Question 22

Non-nucleoside reverse transcriptase inhibitors (nNRTIs)

Answer 22

Bind at different site acting on RT
- 1st generation: efavirenz, nevirapine
- 2nd generation: rilpivirine, etravirine

Question 23

Integrase strand transfer inhibitors (INSTIs)

Answer 23

Inhibit the binding of the preintegration complex (PIC) to host cell DNA, preventing integration of the DNA provirus
- INSTIs bind to Mg2+ & blocks integration into host DNA