Mechanisms of action of antivirals Flashcards

Question

How is aciclovir used to treat VZV?

Answer 1

→Treatment of chickenpox →Treatment of shingles →Prophylaxis of chickenpox

Answer 2

→Activated by Thymidine kinase by increase number of phosphate residues in aciclovir →Looks like DNA base so viral DNA incorporates acyclovir →chain termination

Answer 3

→HSV thymidine kinase (TK) has 100x the affinity for ACV compared with cellular phosphokinases →Aciclovir triphosphate has 30x the affinity for HSV DNA polymerase compared with cellular DNA polymerase →Aciclovir triphosphate is a highly polar compound - difficult to leave or enter cells (but aciclovir is easily taken into cells prior to phosphorylation) →DNA chain terminator

Answer 4

→Inhibits CMV DNA polymerase

Answer 5

→guanosine

Answer 6

→reactivated infection or prophylaxis in organ transplant recipients →congenital infection in newborn →retinitis in immunosuppressed

Answer 7

→aciclovir

Answer 8

→has UL97 kinase

Answer 9

→because of ganciclovir resistance (TK mutants)

Answer 10

→Selectively inhibits viral DNA/RNA polymerases and RTs →No reactivation required →Binds pyrophosphate binding site – a structural mimic

Answer 11

→CMV infection in the immunocompromised

Answer 12

→Chain terminator - targets DNA polymerase Competes with dCTP Monophosphate nucleotide analog

Answer 13

→prodrug | →phosphorylated by cellular kinases to di-phosphate

Answer 14

→drug active against CMV; but MUCH MORE nephrotoxic | Treatment of retinitis in HIV disease

Answer 15

→Thymidine Kinase mutants →DNA polymerase mutants

Answer 16

→drugs not needing phosphorylation are still effective (e.g. foscarnet, cidofovir)

Answer 17

→all drugs rendered less effective

Answer 18

``` →Envelope protein, gp120 with transmembrane gp41 →Membrane- associated matrix protein Gag 17 →Nucleocapsid protein Gag p24 →ds RNA genome →Viral envelope →Nucleocapsid protein Gag p24 →ds RNA genome ```

Answer 19

``` →Attachment with binding of viral gp120 via CD4 and CCRX →2. reverse transcription of RNA into dsDNA →3. Integration into host chromosome of proviral DNA →4. Transcription of viral genes →5. Translation of viral mRNA into viral proteins →. Virus assembly and release by budding →7. maturation ```

Answer 20

→Anti-reverse transcriptase inhibitors →Protease inhibitors →Integrase inhibitors → Fusion inhibitors- gp120/41 - biomimetic lipopeptide →Highly Active Anti Retroviral Therapy HAART

Answer 21

→nucleoside/nucleotide RT inhibitors → non-nucleotide RT inhibitors (allosteric)

Answer 22

→Synthetic analogue of nucleoside thymidine – when converted to tri-nucleotide by cell enzymes, it blocks RT by →competing for natural nucleotide substrate dTTP incorporation into DNA causing chain termination

Answer 23

→Non-competitive inhibitor of HIV-1 RT →Do not look like DNA bases Gets incorporated into viral DNA by RT- terminates production of new viral DNA →Synergistic with NRTI’s such as AZT because of different mechanism

Answer 24

→PEP – within 72 hours post exposure - take for 28 days. | 2x NRTIs + integrase inhibitor

Answer 25

→2x NRTIs (Truvada) two tablets 2 – 24 hours before sex, one 24 hours after intercourse and a further tablet 48 hours after intercourse - called ‘on-demand’ or ‘event based’ dosing

Answer 26

→Mutation rate - high →Viral load – high

Answer 27

→Selection pressure and mutation frequency →Increased mutation rate seen in HIV. →They form a quasispecies within an individual patient

Answer 28

→Inhibit virus uncoating by blocking the influenza encoded M2 protein when inside cells and assembly of haemagglutinin

Answer 29

→Inhibits virus release from infected cells via inhibition of neuraminidase

Answer 30

→target and inhibit NA at highly conserved site (reduce chances of resistance via mutation) →prevent release of sialic acid residues from the cell receptor →preventing virus budding and release and spread to adjacent cells

Answer 31

→zanamivir

Answer 32

→via blood – infectious (mother to baby)

Answer 33

→chronic liver disease

Answer 34

→1 - 6 months

Answer 35

→enveloped; Flaviviridae family

Answer 36

→Block RNA synthesis by inhibiting inosine 5'-monophosphate (IMP) dehydrogenase – →blocks the conversion of IMP to XMP (xanthosine 5'-monophosphate) →thereby stops GTP synthesis and, consequently, RNA synthesis

Answer 37

→RSV →HepC →combination with pegylated interferon

Answer 38

→shorten the length of therapy, →minimize side effects, →target the virus itself, →improve sustained virologic response (SVR) rate

Answer 39

→block replication complex formation assembly

Answer 40

→NS2-3 and NS3-4A proteases | →NS3 helicase and NS5B

Answer 41

→specific Hep B immunoglobulin (passive immunity) →+ vaccination →within 48 hours

Answer 42

→interferon-gamma + ribavarin (anti-viral) for 6 months →within first 2 months of exposure →90% cure rate

Answer 43

→80% protection i.e. no sero-conversion →must be FAST – hours →antiviral drug treatment – 28 days →2xNRTI + protease or integrase inhibitor

Answer 44

``` →rabies →dengue →Common cold viruses →Ebola →HPV →Arbovirsues ```