Flashcards
23 - SARS-CoV-2
Cards in this deck (47)
- 1what kind of nucleic acid is SARS-CoV-2positive sense single stranded RNA
- 2is SARS-CoV-2 envelopedyes
- 3what is SARS-CoV-2 envelope surface glycoprotein that binds to host cellspike protein
- 4what host receptor does the spike protein bind toACE2
- 5what does binding of the spike protein to ACE2 causereceptor-mediated endocytosis
- 6how does the capsid get released from the endosomethe envelope membrane fuses with the endosomal membrane
- 7how does the envelope fuse with the endosomeconformational change upon initial binding of s protein to ACE2 causes fusogenic protein exposure and these embed themselves in the endosomal membrane creating a pore
- 8why does conformational change need to occur before the fusion peptides are able to insert themselvesthey are more internalised so need to be moved to where they can act
- 9ACE2 receptors are found on many cells but SARS-CoV-2 only infects some... what is present alongside ACE2 that makes SARS-CoV-2 enter some cells but not othersthe virus requires hijacking of host proteases for entry into cells
some cells don't have these - 10what are the 3 types of host proteases1. proprotein convertase (furin)
2. cell surface protease (TMPRSS2)
3. lysosomal proteases (cathepsin L (CTSL)) - 11how many proteases does a virus require for fusion1-2
- 12explain how the virus uses host proteases in the receptor mediated endocytosis processspike-ACE2 binding causes endocytosis
furin in the endosome activates s protein
acidification of endosome activates cathepsin L
proteolysis occurs leading to membrane fusion and release of viral RNA into cytoplasm - 13explain how the virus uses host proteases in direct fusion with plasma membranespike protein binds to ACE2
S protein cleaved by furin exposing the fusion peptide containing S2 component
TMPRSS2 cleaves S2 to expose/release fusion peptide -> fusion occurs - 14why are there two pathways of entry that also use two different combinations of host proteasesso that SARS-CoV-2 can enter many cells
if the cell doesn't have cathepsin (lysosomal protease), SARS-CoV-2 enters via direct fusion
if a cell doesn't have TMPRSS2 (cell surface protease) then it enters via receptor-mediated endocytosis - 15once in the cell what does the RNA bind to immediately and whereribosomes in the cytoplasm where is gets translated into a protein
- 16what does this protein need to undergo nextcleavage into smaller proteins
- 17what enzyme conducts this cleavageviral proteases
- 18what specific protein is creates from the RNARNA dependent RNA polymerase
- 19what does this RdRp allow the virus particles to doreplicate their genome
- 20where do these replicated viral RNA and transcribed viral proteins goin double membrane bound compartments like ER and vesicles
- 21what is the complex called when proteins and RNA are all packaged into the ER or a vesiclereplicase transcriptase complex
- 22describe the assembly of a new virionvesicle with structural/capsid proteins on its surface engulfs the replicated RNA and assembles it inside the vesicle giving it its envelope membrane as well as still encompassing it in the vesicle membrane
- 23how is SARS-CoV-2 released from host cell once assembledexocytosis
- 24what does RNA translation/synthesis of the SARS-CoV-2 producenon structural proteins e.g. RdRp
structural proteins e.g. spike protein + capsid - 25where does assembly of viral proteins occur before they are then assembled around the replicated RNAtranslocated to ER-golgi intermediate compartment
- 26discuss how the RdRp replicates the ss(+)RNARdRp uses positive sense ssRNA strand as a template to create a complementary negative sense ssRNA strand
which it then uses as a template to create lots of positive sense ssRNA strands - 27what does this process also lead to accumulation of and whymutations because RdRp doesn't have proof reading so is error prone and inaccurate
- 28what would be the outcome of a deletarious mutationcould cause deletion of function properties and therefore result in a dysfunctional/non-functioning virus
- 29why do viruses tend to keep their genomes smallbecause the larger the genome the more likely they are to acquire a deletarious mutation
- 30why is viral RNA so prone to mutation (3 reasons)RNA is unstable
RdRp doesn't have proof reading
incomplete viral genome replication - 31explain why RNA is unstablesingle stranded meaning bases are exposed/vulnerable to damage
e.g. environment like immue system/drugs can cause alkylation or deamination of bases - 32explain the incomplete viral genome replicationthe whole genome is not replicated - it just recombinates with viral genomes in the same cell until they have the whole genome -> error prone system
- 33through what ways does SARS-CoV-2 accumulate mutations (3 things)antigenic drift
host mediated RNA editing (C-U changes)
accumulation through recombination - 34explain what is meant by accumulation of mutations in SARS-CoV-2 through recombinationif there is two variants of SARS-CoV-2 in the cell and both are incomplete they combine to complete the genome and this can cause accumulation of mutations
- 35what unique things does SARS-CoV-2 have and do that lowers the error rate 15-20 foldit has an exonuclease enzymes NSP14 which proof reads and corrects any incorrect bases laid down by RdRp - like the proof reading in human cells
- 36so explain in terms of mutation acquisition the distinct but different strains of SARS-CoV-2 that emergedthere were different strains that occured through higher replication when advantageous mutations were created
but each strain was relatively unique due to lack of mutations thanks to the proof reading NSP14 (alpha, beta, delta) - 37explain the advantageous mutations and the strain progression of SARS-CoV-2different strains emerged due to acquisition of advantageous mutation so once an advantgeous mutation was acquired that strain quickly took over from the previous strain
- 38explain the change in conformation of the spike protein through activationinactive it was downward conformation
when active it became upward receptor binding formation - 39what mutation occured causing the alpha variant to arisemutation that allowed constant upward/receptor binding conformation of the spike protein allowing for quicker easier binding and therefore transmission
- 40but what did this mutation allow for that was advantageous to scientists/our immune systemconsitent upward conformation exposed an area of conserved structure (spike protein) to which antibodies could be produced/designed to target for neutralisation
- 41as well as mutations to the spike protein where else did mutations occur that was advantageous to the SARS-CoV-2 virusS1/S2 furin cleavage site
- 42what did this mutation to s1/s2 furin cleavage site cause in the spike proteinincreased positive charge
increased tissue tropism
was able to spread to/infect different tissues and increased cleavage of S1/S2 at airway epithelial cells - 43name a non-spike protein mutation that occured giving advantage to virusproduction of interferon antagonist protein
able to shut off inate immune response as interferons are involved in host antiviral response - 44overall what did all of these mutations give the virusincreased infectibility, increased severity, change in antiviral susceptibility, change in susceptibility to antibodies
- 45what do different strains havedifferent mutations
- 46what do these different mutations mean for vaccinessome were more effective on certain strains than others
- 47what could a mutation to SARS-CoV-2 mean for vaccinationsudden resistance to vaccines
Information
- Description
- Year 2 Biomedicine Year 2 (Immunity and infection ) Flashcards on 23 - SARS-CoV-2 , created by Georgie Philpott on 07/01/2023.
- Created by
- Georgie Philpott · Jan 2023
- Updated
- Jan 7, 2023
- Views
- 0
- Rating