ANTIVIRAL CHEMOTHERAPY

• AMANTADINE and RIMANTADINE:
• ACTION: Inhibits the uncoating stage (part of binding) of Influenza A virus.
• Binds to M-Protein and blocks the pre-lysosomal uncoating, after attachment has already taken place.
• Viruses can acquire resistance with extended use.
• VIRUSES: Inhibits primarily the Influenza A virus, but also has activity against Influenza C, Sendai, Dengue, and Rubella viruses.
• Parainfluenza 1,2,3, Influenza B, and RSV are resistant
• SIDE-EFFECTS: In 10% of patients, CNS toxicity, nervousness, difficulty concentrating.
• CLINICAL: Use is restricted to certain subgroups: in epidemics, at-risk patients, hospitalized patients.
• RIBAVIRIN:
• ACTION: Inhibits viral transcription, by binding to and inhibiting enzymes involved in nucleic acid metabolism. Specifically inhibits inosine monodehydrogenase, involved in the synthesis of GTP.
• SIDE-EFFECTS: It is toxic in that it does not discriminate well between host cell and virus. Toxic to liver cells and can cause anemia.
• VIRUSES: RSV in infants, and Lassa Fever intravenously.
• ACYCLOVIR:
• ACTION: It is converted by HSV viral Thymidine Kinase into a monophosphate activated form. Host cell then converts monophosphate form into triphosphate form. This form then does two things:
• Binds and inhibits viral DNA polymerase
• It is incorporated into viral DNA, where it acts as a chain-terminator.
• RESISTANCE in HSV is due to mutations in two different viral proteins:
• Viral Thymidine Kinase, preventing conversion of acyclovir to the triphosphate form.
• Viral DNA polymerase, such that it doesn't bind the drug.
• VIRUSES: Specific for HSV infections: HSV-1, HSV-2, VZV, but not CMV or EBV.
• Resistance can occur, due to mutations in either Thymidine Kinase or viral DNA polymerase.
• ADENINE ARABINOSIDE (Ara A):
• ACTION: Binds to DNA-Polymerase -- cellular or viral, thus bad side effects.
• VIRUSES: Used to be used for HSV-Encephalitis cases. Now surpassed by Acyclovir.
• GANCICLOVIR:
• VIRUS: CMV, promising new treatment. Also works on HSV.
• Up to 80% of HIV patients will relapse if therapy is discontinued. CMV pneumonia does not respond as well as other CMV infections.
• ACTION: Nucleoside analog of guanosine, similar to Acyclovir.
• SIDE-EFFECTS: Reversible neutropenia, liver and CNS toxicity.
• AZIDOTHYMIDINE (AZT, ZIDOVUDINE):
• ACTION: Inhibits Reverse Transcriptase.
• AZT is phosphorylated first by host enzymes.
• VIRUS: HIV-1