Lecture 14: Antivirals and antifungals

Question 1

Cell wall of fungi contains?

Answer 1

Chitin
only organism with both chitin and glucan in cell wall

Question 2

Thioredoxin

Answer 2

drugs that bind to thioredoxin inhibit GRX2 gene, inhibit redox signalling in fungi

Question 3

Amphotericin B

Answer 3

directly binds to ergosterol in fungal cell membrane
cause leakage
fungicidal

not orally bioavailable, must be injected
low TI (can bind to cholesterol)
side effects: hypotension, anorexia, kidney/liver damage

Question 4

Nystatin

Answer 4

broad spectrum
directly binds to ergosterol and cause leakage
fungicidal

not oral bioavailable
good safety profile
only useful in skins and GI

Question 5

Fluconazole

Answer 5

interacts with 14-demethylase that catalyzes lanosterol into ergosterol
cause leakage
fungicidal

safe in humans because human use HMG-CoA reductase
water soluble and highly bioavailable, broad spectrum, oral or IV

Question 6

Griseofulvin

Answer 6

binds to alpha and beta tubulin, block mitosis and replication
fungistatic

give orally, can be used as anti-cancer drug

Question 7

Flucytosine

Answer 7

PRODRUG
converted by cytidine deaminase to 5-FU
5-FU to 5-FdUMP, block RNA/DNA synthesis
fungistatic

Question 8

Viral episome

Answer 8

interact with host genome permanently but not integrating

Question 9

Docosanol

Answer 9

directly insert into human cell membrane
inhibit fusion of viral envelope to host cell membrane

not orally bioavailable
only useful for topical infections

Question 10

Acyclovir

Answer 10

PRODRUG
thymidine kinase in virus converts drug into triphosphate NTP
integrates into DNA cause chain termination

generally safe unless activated in non-infected cells

Question 11

Zidovudine

Answer 11

PRODRUG
converts in triphosphate form by thymidine kinase
inhibit reverse transcriptase
chain termination

orally available
USED FOR HIV (retrovirus contains reverse transcriptase)

Question 12

Nirmatrelvir

Answer 12

inhibit 3C-like protease of SARS-CoV-2
competitive inhibitor that blocks viral replication

orally available and well-tolerated, REBOUND in 1 out of 3 people

Question 13

Amantadine

Answer 13

use against influenza A
block M2 ion channels in viral envelope
important in viral coating
block replication

resistance if M2 ion channel mutated
teratogenic

Question 14

SARS-CoV-2

Answer 14

ssRNA virus
uses RNA-dependent RNA-polymerase for replication
29 unique proteins in virus
spike glycoprotein binds to ACE-2 receptors on surface of cells

Question 15

Pfizer/Modern COVID RNA vaccines

Answer 15

use lipid nanoparticles to package modified RNA (pseudouridine) encoding spike protein
targets dendritic cells

Question 16

Resistance to COVID vaccines

Answer 16

mutated epitopes on spike protein
reduce vaccine efficacy

Question 17

3 steps in producing recombinant and engineered antibodies

Answer 17

1. identify antibody
2. immunize rabbit and collect serum
3. increase production

Question 18

5 ways of monoclonal antibodies as antivirals

Answer 18

1. binds to host viral receptor to block entry
2. opsonization
3. binds to viral epitopes
4. stimulate secondary cells
5. B,T cell activation

Question 19

Palivizumab

Answer 19

bind to protein in RSV envelope and blocks fusion

Question 20

Ibalizumab

Answer 20

binds to T-cell receptor and block HIV entry

Question 21

REGEN-COV

Answer 21

contains 2 mAbs
bind separate epitopes of COVID spike and prevent interactions with ACE-2 receptors

Question 22

Cas9 to treat HIV

Answer 22

HIV is an integrated retrovirus
disrupt key replication gene, or fully cut out HIV provirus from genome

Question 23

Cas13 for SARS-CoV-2 treatment

Answer 23

Cas13 can cleave viral RNA and block replication

Question 24

How does virus escape CRISPR

Answer 24

mutation in PAM spacer sequence
repair process after cut can cause mutation and viral escape

use multiple guide sequence with degenerate bases