Antivirals

Question 1

virus

Answer 1

obligate intracellular parasite: rely on host biosynthetic machinery to reproduce
exist as independent particles when not inside an infected host (virions)
encode ~4-200 proteins

Question 2

virions

Answer 2

double or single stranded DNA or RNA
a protein coat (capsid)
some have a lipid envelope derived from the host cell - may contain antigenic glycoproteins

Question 3

viral range

Answer 3

group of cell types or species a virus can infect

not a lot of cross-species viruses

Question 4

viral shape

Answer 4

classified based on shape of capsid
- helical
- icosahedral
- complex

Question 5

pathogenicity

Answer 5

ability of viruses to cause disease

degree of pathogenicity is virulence (how strong of an infection they cause)

Question 6

varicella zoster

Answer 6

chicken pox is the primary V2V infection - presents with blisters
virus is dormant in host - V2V latency (in dorsal root ganglia)
reactivation of virus = shingles

chronically infected = carriers

Question 7

viral replication cycle

Answer 7

absorption, penetration, replication, release

proteins on surface of virus bind to receptor protein on host cell → interaction determines the host range of virus + begins infection
viral DNA/RNA crosses plasma membrane to cytoplasm or nucleus → interacts with host machinery to translate the DNA/RNA into viral protein
newly synthesized virion particles are released to continue infection cycle

Question 8

central dogma of biology

Answer 8

DNA → mRNA → protein
DNA can be transcribed into mRNA or replicated (in the nucleus)
protein translation (mRNA → protein) happens in the ribosomes - cytoplasm

Question 9

DNA viruses

Answer 9

enter the host cell nucleus → viral DNA is integrated into host genome and transcribed into mRNA - host DNA-dependent RNA polymerase
mRNA is translated into viral proteins
further replication of viral genome requires DNA-dependent DNA polymerase

virus uses host machinery (exception: poxviruses - carry own and replicate in cytoplasm)

Question 10

RNA viruses

Answer 10

double stranded - bring own machinery: RNA-dependent RNA polymerase → transcriptase and replicase
most replicate in cell cytoplasm

Question 11

retroviruses

Answer 11

RNA genome directs formation of DNA molecule
RNA→DNA→mRNA→protein

viral enzyme - reverse transcriptase is RNA-dependent DNA polymerase → copies viral RNA into DNA
viral DNA is integrated into host DNA → host enzymes take over

Question 12

vaccinations

Answer 12

cheap + effective way of preventing viral infections
consist of live-attenuated or killed viruses, or viral proteins or mRNA (antigens)

Question 13

anti-virals

Answer 13

drugs that interfere with stages of viral replication → viral entry, nucleic acid synthesis, protein synthesis, viral packaging, virion release

combination therapy → greater clinical effectiveness + delay of resistance

virustatic: only active against replicating viruses and don’t affect latent virus (effect is on replication cycle)

Question 14

acyclovir

Answer 14

anti-herpes drug
nucleoside analog = DNA chain termination → virus incorporates into genome during replication = halts life cycle

must be phosphorylated to acyclovir-triphosphate to be incorporated into viral DNA as a terminal substrate
enzyme specific to herpes simplex virus (thymidine kinase) adds first phosphate group

Question 15

acyclovir resistance

Answer 15

can result from:
- impaired production of viral thymidine kinase
- altered thymidine kinase substrate specificity (e.g. phosphorylation of thymidine but not acyclovir)
- altered viral DNA polymerase

Question 16

HIV

Answer 16

human immunodeficiency virus
lentivirus → retrovirus that leads to chronic persistent infection with gradual onset of clinical symptoms

HIV infects human immune cells (CD4+ T cells)

replication is constant following infection

Question 17

AIDS

Answer 17

acquired immunodeficiency syndrome

CD4+ T cells decline below a critical level → cell mediated immunity is lost and body becomes susceptible to opportunistic infections
death is caused by infections that would normally be mediated by immune system

Question 18

anti-viral HIV drugs

Answer 18

target viral infection at multiple levels: fusion, transcription, integration into host genome, virion release
usually combine 3+ antiretroviral drugs

highly active antiretroviral therapy (HAART) - drug combinations that can slow or reverse the increases in viral RNA load that normally accompany progression of disease

Question 19

entry inhibitors

Answer 19

HIV infection begins with attachment of HIV envelope proteins called gp120 to CD4 and CCR5 receptors on surfaces of T cells → binding allows entry

entry inhibitors interfere with binding, fusion, and entry of HIV virion into human cell

Question 20

Maraviroc

Answer 20

CCR5 receptor antagonist
interferes with HIV binding to T cell
entry inhibitor

Question 21

reverse transcriptase

Answer 21

HIV enzyme that synthesized DNA from HIV RNA using nucleosides in the host T-cell
RNA dependent DNA polymerase

Question 22

nucleoside reverse transcriptase inhibitors

Answer 22

small molecule drugs that are similar to the host cell nucleosides and are incorporated into new HIV DNA chain as if they were endogenous molecules
only incorporated by reverse transcriptase (does not affect mammalian polymerases)

lack a 3’hydroxyl group on ribose ring = impossible to attach next nucleoside → chain termination

Question 23

integrase strand transfer inhibitors

Answer 23

integrase is a viral enzyme that inserts viral genome into the DNA of the host cell

integrase inhibitors block the action of integrase to inhibit HIV proliferation

ex. Raltegravir

Question 24

aspartate proteases

Answer 24

enzyme that cleaves precursor proteins to form the final structural proteins of the mature virion core
critical in assembly of infectious HIV virions

Question 25

HIV protease inhibitors

Answer 25

designer drugs based on molecular characterization of the active site of the viral enzyme
block new HIV from becoming mature by inhibiting aspartate protease ability to cleave viral protein

usually used in combination with reverse transcriptase inhibitors

Question 26

M2 protein

Answer 26

functions as a proton ion channel required at the onset of infection to permit acidification of the virus core, which in turn activates viral RNA transcriptase

Question 27

amantadine

Answer 27

anti-influenza drug
inhibit an early step in replication of the influenza A virus (viral uncoating as virus enters host cell)

amantadine blocks proton (H+) transfer through M2, thus blocking acidification and the initiation of viral transcription

prophylactive against influenza A (not B) → reduce duration of symptoms if given within 48 hr after contact
H3N2 = resistant influenza A mutant
vaccination → cost-effective means of reducing disease burden

Question 28

neuroaminidases

Answer 28

produced by influenza A and B
enzymes cleave sialic acid residues from viral proteins that enables virus to be released from the host cell

Question 29

zanamivir

Answer 29

neuroaminidase inhibitor - targets last phase of replication cycle
= impede viral spread