Antivirals Flashcards
Acyclovir
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)
Ganciclovir
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
Cidofovir
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
Foscarnet
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
HBV nucleotide analogs
Tenofovir - adenine analog
Entecavir - deoxyguanosine analog
Peginterferon-α2a for HBV
Activates type 1 Interferon in hepatocyes that;
limit protein synthesis and induce viral mutagenesis
* Increases MHC-1 expression on infected cells
Ribavirin (HCV)
Older therapy; Guanosine analog that depletes pools of guanosine triphosphate
Protease inhibitors in HCV
NS3/NS4A protease inhibitor
NS5a inhibitor more potent and less likely for mutants
Adamantanes
Influenza drug
* Inhibits M2 - intereres with uncoating
only works for influenza A
Neuraminidase inhibitors
Oseltamivir (Tamiflu)
*Prevents entry back inhibiting neuraminidase
* Neuraminidase cleaves sialic acid receptor allowing entry
Baloxavir marboxil
Influenza
Inhibits PA subunit of RNA polymerase
- Eliminates use of host mRNA caps for viral mRNA synthesis
Ribavirin for RSV
Guanosine analog that induces excess number of mutations
* Also depletes GTP pool
* Used for immunocompromised patients
* active against DNA and RNA viruses
Palivizumad
RSV prophylaxis
* Monoclonal antibody - epitope of F protein
Paxlovid (ritonavir-boosted nirmatrelvir)
Nirmatrelvir = protease inhibitor
Ritonavir = protease inhibitor & cytochrome P450 (CYP) 3A4 inhibitor
Remdesivir
adenosine analog; stalls RdRp resulting in chain termination
Molnupiavir
Prodrug (N4-hydroxycytidine, NHC) is metabolized in cells to yield a triphosphate form (NHC-TP)
- Competes with CTP or UTP
Anti-SARS-CoV-2 monoclonal antibodies
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
Antiretroviral Entry inhibitors
Temsavir, binds to HIV gp120 and prevents normal attachment of the host CD4
Ibalizumab - prevents gp120 conformational change for binding
CCR5 inhibitor – Maraviroc
Binds to host CCR5 - preventing HIV binding
- not used for initial therapy
- need to check for affinity to CXCR4
Fusion inhibitor – Enfuvirtide
Blocks gp41 conformational change by preventing interaction between HR1 and HR2 regions
- not used for initial therapy
Nucleoside reverse transcriptase inhibitors (NRTIs)
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
Non-nucleoside reverse transcriptase inhibitors (nNRTIs)
Bind at different site acting on RT
- 1st generation: efavirenz, nevirapine
- 2nd generation: rilpivirine, etravirine
Integrase strand transfer inhibitors (INSTIs)
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
