Antiviral Agents Flashcards
(33 cards)
What are the general mechanisms by which antivirals work?
Disrupt viral structure or block a virus-specific activity (enzymes, attachment, viral replication)
Acyclovir is a common herpesvirus antiviral. What is the mechanism of action?
Acyclovir acts as a guanosine analog. A viral enzyme adds the first phosphate group required to activate the drug. It then competitively competes for integration into the DNA chain and terminates replication.
What antiviral is used primarily to treat HSV?
Acyclovir - May also be used for Varicella, but less effective
How have viruses developed resistance to acyclovir?
Loss of the gene encoding thymidine kinase (required for antiviral activation), mutation in the kinase reducing affinity for acyclovir, mutation in viral DNA polymerase that inhibits acyclovir binding
What is Ganciclovir used to treat?
Generally CMV, but also used for HSV, VZV, HHV6, HHV8
What is the mechanism of action of Ganciclovir?
Guanosine analog phosphorylated by a protein kinase phosphotransferase resulting in termination of chain elongation. The drug can also be phosphorylated by host enzymes.
What CMV gene encodes a protein kinase phosphotransferase utilized to activate Ganciclovir?
UL97
How have viruses developed resistance to Ganciclovir?
Mutations in UL97 that prevent drug phosphorylation, mutations in DNA polymerase that decrease affinity for drug
Cidofovir is a cytidine analog. How does the antiviral differ from other nucleoside analogs?
The drug has the first activating phosphate attached. The second and third phosphates are added by cellular enzymes meaning the drug is present in both infected and unaffected cells
What is the clinical usage of Cidofovir?
Primarily CMV in AIDS patients - Also for CMV, HSV-1, HSV-2, VZV, EBV, HHV-6, HHV-8, adenovirus, HPV
What is Foscarnet? What is its mechanism of action?
Pyrophosphate analog that binds the DNA polymerase and HIV reverse transcriptase and stops DNA synthesis
What is the clinical usage of Foscarnet?
Ganciclovir-resistant CMV, acyclovir-resistance HSV or VZV
Some anti-HBV drugs manipulate the immune response. How is this possible?
The drug binds and activates interferon receptors on hepatocytes, activating expression of IF-stimulated genes. These also increase MHC-I expression on affected cells.
Tenofovir and Entecavir are FDA-approved anti-HBV drugs. How do they work?
Tenofovir is an adenine analog that targets the reverse transcriptase and does not need phosphorylation for activation.
Entecavir is a deoxyguanosine analog that must be phosphorylated for activation.
How does HCV therapy differ from that of HBV?
HBV therapy is meant to manage the virus. HCV anti-virals are intended to eradicate the virus and maintain undetectable levels.
What are the 5 classes of anti-retroviral drugs?
Attachment/Entry Inhibitors, Nucleoside Reverse Transcriptase Inhibitors (NRTIs), Non-Nuecloside Reverse Transcriptase Inhibitors (NNRTIs), Integrase Strand Transfer Inhibitors (INSTIs), Protease Inhibitors
Temsavir is an anti-retroviral entry inhibitor. What is the mechanism of action?
Binds to hp120 and prevents attachment to the CD4 receptor
Ibalizumab is a monoclonal antibody for ART. What is the mechanism of action?
Binds to CD4a, preventing the required conformation change when gp120 binds the receptor
Maraviroc is an anti-retroviral entry inhibitor. How does it work?
Binds CCR5 and alters the conformation to prevent HIV binding. The drug is ineffective against CXCR4 viruses and may lead to selection for viruses that bind X4.
How is HIV fusion with the host cell inhibited?
Enfuvirtidae binds to gp41. This blocks the conformational change that occurs after gp120 binds CD4 and prevents gp41 from mediating fusion.
Nucleoside reverse transcriptase inhibitors (NRTIs) are used as the first ART for HIV. How does the drug work?
Nueclosides requires phosphorylation for action and then bind the reverse transcriptase and terminate chain elongation
How does the mechanism of Non-nucleoside reverse transcriptase inhibitors differ from nucleoside reverse transcriptase inhibitors for ART?
Non-nucleoside reverse transcriptase inhibitors target the reverse transcriptase, but bind at a site distinct from the active sight and inhibit binding of new nucleotides. The drug does not act as a nuceloside and does not need to be phosphorylated for activation. Resistance is distinct from that against NRTIs.
What is the mechanism of integrase strand transfer inhibitors?
Bind to Mg2+ to inhibit binding of the preintegration complex to host DNA. This blocks the DNA provirus from being integrated into host DNA. Resistance is uncommon.
What is the mechanism of ART protease inhibitors?
Bind the enzymatic pocket of the HIV protease and inhibit function. This prevents maturation of the virus to an infectious particle. This ART is used for patients failing other regiments as resistance is uncommon.
