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Clinical Pathology > Antivirals > Flashcards

Flashcards in Antivirals Deck (16)
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What types of genes do viruses possess?

Structural and metabolic


What kind of polymerase would be required by a DNA virus?



What kind of polymerase would be required by a RNA virus.

RNA to RNA - virus must encode this itself


What kind of polymerase would be required by retroviruses and Hep B?

RNA to DNA aka reverse transcriptase - encoded by virus


What is the mode of action of azidothymidine (AZT)?

Nucleoside Reverse Transcriptase Inhibitor (NRTI)


Give examples of other NRTIs.

Pyrimidine analogues
- Thymidine analogues
- Zidovudine
- Cytosine analogues
- Lamivudine

Purine analogues (Adenine and Guanidine)
- Abacavir
- Tenofovir


Why do the antiretrovirals Lamividine and Tenofovir work against the Hep B virus?

Because Hep B also encodes reverse transcriptase.


Give examples of non-nucleoside reverse transcriptase inhibitors.



How do fusion inhibitors work to block HIV infection e.g enfuvirtide.

HIV binds to the host CD4+ cell receptor via the viral protein gp120; gp41, a viral transmembrane protein, then undergoes a conformational change that assists in the fusion of the viral membrane to the host cell membrane. Enfuvirtide binds to gp41 preventing the creation of an entry pore for the capsid of the virus, keeping it out of the cell.


How do protease inhibitors work?

Prevent viral replication by selectively binding to viral proteases (e.g. HIV-1 protease) and blocking proteolytic cleavage of protein precursors that are necessary for the production of infectious viral particles.


How do NNRTIs work?

Do not bind to the active site of the polymerase but in a less conserved pocket near the active site in the p66 subdomain. Their binding results in a conformational change in the reverse transcriptase that distorts the positioning of the residues that bind DNA, inhibiting polymerization.


How do NRTIs work?

Pyrimidine/purine nucleoside analogues cause premature chain termination during reverse transcription.


What is HIV integrase?

Combines with viral DNA and other cellular cofactors to form the preintegration complex (PIC). Subsequently, the integrase enzyme removes a nucleotide from each 3’ DNA terminus, thereby exposing reactive hydroxyl groups. The PIC then enters the host cell nucleus where it binds to host cell DNA. Integrase nicks each strand of the host cell DNA and exposes the 5’ phosphate groups, enabling covalent bonding of host and viral DNA. After this strand transfer is complete, host cell enzymes repair gaps between the viral and host DNA.


How do integrase inhibitors work?

Target the strand transfer step of viral DNA integration and are sometimes referred to as “INSTI” (integrase strand transfer inhibitor) drugs. These drugs prevent or inhibit the binding of the pre-integration complex to host cell DNA, thus terminating the integration step of HIV replication.


What is highly active antiretroviral therapy and when is it started?

2 NRTIs + NNRTI or 2 NRTIs + boosted PI
Started when CD4 count falls.


How was the first HIV cure achieved?

- HIV suppressed on antivirals
- Existing CD4 lymphocytes destroyed by conditioning
- Stem cells reconstituted with HLA-matched but delta 32 homozygous allogeneic donor
- Antiviral therapy stopped following transplantation
- Remained HIV negative (by PCR)
- HIV antibody titres have declined

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