28. Coronavirus 2 Flashcards
(50 cards)
why are spikes under immune selection?
immune pressure from Ab causes spikes to mutate
initial monoclonal antibody therapy
used COVID-19 convalescent plasma that has Ab from patient who had recovered from infection
2 examples of therapeutics MAb
- Bamlanivimab
- Bebtelovimab
describe Bamlanivimab
used as early therapy but the virus evolved so became ineffective
describe bebtelovimab
used as early therapy for patients with high risk of disease progression
3 benefits of MAb therapies
- good safety
- moderate efficacy
- good for emergency use when no drugs or vaccines are available
3 downsides of MAb therapies
- resistance mutations in spike
- variants have many mutations that make Ab not effective
- vaccines are better
what was another consideration that had to be made in addition to developing a vaccine that allows the body to make spike proteins?
had to make sure the immune system didn’t react to mRNA
what are the 2 fates of genomic +RNA
- +RNA copied into -RNA for replication
- +RNA copied into subgenomic -RNA
role of subgenomic RNA
to make structural and accessory proteins
mechanism of producing subgenomic -RNA
when viral RNA pol makes -RNA, it can stop at TRS-B btwn each protein and switch back to the leader TRS-L, giving short pieces of -RNA
what does TRS stand for?
transcription regulatory system
4 proteins in RNA replication/transcription complex
- NSP7
- NSP8
- NSP12
- NSP13
what is the most important protein in RNA replication/transcription complex?
NSP12 –> RdRP
role of NSP13?
sits at the top of the complex –> RNA helicase to open up dsRNA for RNA synthesis
what is the role of NSP14? why do we need it?
NSP14 = proofreader
needed bc long genome allows for mutations
what is the co-factor for NSP14?
NSP10
2 activities of NSP14
- 3’ to 5’ EXOribonuclease
- adds methyl group to cap on mRNA
why does the viral RNA have a cap? (2)
- improve viral protein translation
- avoid host immune detection
what are the 2 viral RNA capping enzymes?
both add a methyl:
nsp14 –> guanine-N7 methyltransferase
nsp16 –> 2’ methyltransferase
what happens if NSP16/NSP14 is mutated and there is a bad RNA cap?
body can shut down the virus
what is REMDESIVIR?
Chain terminator –> nt analog that is added to the chain but has no OH so no new nt can be added
targets RdRP
what is MOLNUPIRAVIR?
Increases frequency of viral RNA mutations and impairs replication
how does molnupiravir work?
RdRP uses the drug as a substrate instead of CTP or UTP –> incorrectly incorporates G or A leading to mutation