3 - Antivirals Flashcards
Clinical latency in HIV
CD4 T cell count dropping while HIV RNA slowly rising. When HIV RNA exceeds CD4 cells you get onset of symptoms
Acute virus examples
Influenza, measles, mumps, hep A
Chronic latent viral examples
Herpes simplex, cytomegalovirus
Chronic persistent viral occurrences
HIV, Hep B, Hep C
Virus structure
nucleic acid (DNA or RNA)
Protein coat
Sometimes lipid envelope
Viral replication process
Virus attachment to cell (via receptor) Cell entry Virus uncoating Early proteins produce viral enzymes Replication Late transcription/translation - viral structure proteins Virus assembly Virus release
Virus life cycle
Virus take over much of host cell
All viruses encode unique proteins vital for viral replication and infectivity
These unique proteins are targets for molecular inhibition
DNA to DNA requirements
Euk
Dna viruses
DNA to RNA
Euk
DNA viruses
RNA to RNA
RNA viruses
RNA to DNA
Retroviruses (HIV)
Hep B
What is azidothymidine?
AZT
Developed in 1965 as anticancer drug
In 1985 found to inhibit HIV replication
Nucleoside reverse transcriptase factor
What does NRTI stand for?
Nucleoside reverse transcriptase inhibitors
Types of NRTIs
Pyrimidine analogues
Purine analogues
E.g. of pyrimidine analogues
Pyr:
Thymidine - zidovudine
Cytosine - lamivudine
Pur:
A & G - abacavir, tenofovir
E.g. of newer HIV drugs
Non-nucleotide reverse transcription inhibitors (NNRTI)
Protease inhibitors
Fusion inhibitors - enfuviritide (T20)
Integrase inhibitors - raltegravir
Chemokine receptor antagonists - maraviroc
To overcome resistance we have to use which type of therapy
Highly active antiretroviral therapy (HAART)
What is involved in HAART?
2 NRTIs + NNRTI 2 NRTIs + boosted PI Started when CD4 falls Switches off viral replication Take forever Suppression occurs after 10 years
HIV cure
HIV suppressed on antivirals
Existing CD4 lymphocytes destroyed by conditioning
Stem cells reconstituted with HLA-matched but delta 32 homozygous allogenieic donor
Antiviral therapy stopped following transplant
Remained HIV negative (by PCR)
Hep C virus cures
Interferons and ribavirin cure rates of 40-90% depending on viral genotype
Last 3 years have increasing number of directly acting antivirals against various viral proteins
We now have 90% interferon free regimens for all strains
Aciclovir
For Rx (prescription) of Herpes simplex virus (HSV) and Varicella zoster virus (VZV)
Ganciclovir
Cytomegalovirus (CMV)
Oseltamivir and Zanamavir
Neuraminidase inhibitors
Influenza
Ribavirin
Hep C and RSV
Interferons
Hep C and Hep B
