DDT 20 - Anti-retroviral drugs for the treatment of AIDS

Question 1

nucleoside

Answer 1

one of the building blocks to make RNA and DNA

Question 2

HIV treatments

Answer 2

protease inhibitors
reverse transcriptase inhibitors
integrase inhibitors (optionally)
CCR5 receptor antagonist

Question 3

How does HIV enter lymphocytes

Answer 3

HIV binds to 2 different receptors of lymphocytes
primary receptor - CD4
second receptor - CCR5 transmembrane protein, loops thru the cell membrane of T cell 7 times
HIV must bind to both receptors to infect cell

Question 4

what events take place once HIV enters the cell

Answer 4

HIV viral RNA and the contents are empties into the host cell.
HIV takes over and makes many copies of itself

Question 5

Reverse transcriptase function

Answer 5

enzyme that reads viral RNA entered in the host cell and transcribes the sequence into a complementary DNA sequence.

Question 6

why are not all viruses alike

Answer 6

reverse transcriptase makes many mistakes when reading viral RNA sequence
may have different shape surface coat

Question 7

function of integrase

Answer 7

helps insert the viral DNA transcribed from viral RNA into the host. Once the viral DNA is part of the host’s DNA it is called provirus

Question 8

how many genes does HIV RNA have and what is the purpose of these genes

Answer 8

There are nine genes in the HIV RNA. These genes have all the necessary codes to make structural (viral envelope and core) proteins and enzymes (reverse transcriptase, integrase, and protease).

Question 9

viral protease function

Answer 9

The translated viral RNA is made into a long polypeptide sequence which is made up of several individual proteins. These sections must be cut from the long polypeptide chain in order for the proteins (enzymes) to be functional.

Question 10

assembly

Answer 10

viral RNA proteins leave the host cell taking the T-cell membrane containing viral surface proteins

Question 11

name the 3 nucleoside reverse transcriptase inhibitors

Answer 11

azidothymidine (zidovudine)
stavudine (D4T)
abacavir (ABC)

Question 12

Mechanism of action for azidothymidine and thymidine

Answer 12

lack 3’ OH on cyclic sugar

termination DNA chain elongation occurs

Question 13

Non Nucleoside Reverse. Transcriptase Inhibitors (NNRTI) - Nevirapine

Answer 13

Nevirapine binds directly to RT. Thus it blocks RNA and DNA dependent polymerase activities disrupting the enzyme active site.

Question 14

where does the nevirapine bind to?

Answer 14

These inhibitors have been shown to bind in a pocket formed between two beta-sheets of the p66 palm, ~10 Å away from the polymerase active site

Question 15

is nevirapine hydrophilic or hydrophobic and name the amino acids it is made out of

Answer 15

The internal surface of this pocket is predominantly hydrophobic, being constructed primarily from leucine, valine, tryptophan and tyrosine residues.

Question 16

another example of NNRTI

Answer 16

Efavirenz

Question 17

How active is efavirenz and what kind of HIV does it work against?

Answer 17

Very active, also against wild type and resistant mutant of HIV-1.
It gives virus inhibition of 95%.

Question 18

name HIV protease inhibitors

Answer 18

SAQUINAVIR, RITONAVIR, INDINAVIR are competitive antagonists of the natural substrate peptide

Question 19

how does protease inhibitors work

Answer 19

The protease inhibitor binds to the site that normally binds the
protein chain. Once the inhibitor binds the protease cannot bind the
protein to be cleaved and is not functional.

Question 20

what allows protease inhibitors to bind to protease

Answer 20

Protease inhibitors resemble the protein chain that the protease cuts

Question 21

integrase inhibitors function

Answer 21

These compounds are designed to inhibit the Viral Enzyme Integrase, responsible for the integration of the Viral DNA in the Cell genome

Question 22

integrase inhibitors examples

Answer 22

elvitegravir
dolutegravir
GS9160
PICA

Question 23

compounds of name integrase inhibitors contain

Answer 23

Compounds of this class contain a b-ketoester or b-ketoamide

Question 24

how do integrase inhibitors prevent the function of integrase

Answer 24

These compounds enter in the enzyme and go and coordinate to two essential Mg2+ cation that are involved in the catalytic cycle

Question 25

give an example of a CCR5 Antagonist

Answer 25

Maraviroc

Question 26

Maraviroc

Answer 26

Selectively binds to the human chemokine receptor CCR5, which is present on the cell membrane. This binding prevents the interaction of HIV-1 with CCR5-tropic HIV-1 and thereby inhibits the virus from entering the cell