MSI Covid-19 Flashcards
Coronavirus is a positive, single-stranded ___ virus
RNA
Highly pathogenic strains of Coronavirus are from the Genus Betacoronavirus and the subgenus ____________ (MERS-CoV) or subgenus ___________ (SARS Cov and SARS Cov2)
Merbecovirus , Sarbecovirus
Hcov-HKU1 is a type of Coronavirus that often causes sx of the common cold, but if it progresses it can lead to ______________.
pneumonia
The structural protein _____________ protein is bound to RNA genome to make up the nucleocapsid. This helps to generate the actual structure of the virion. Interacts with the RNA and allows assembly and packaging of that genome into this environment.
nucleocapsid (N)
The _______ protein is critical for binding of host cell receptors to facilitate entry of host cell
spike (S)
The __________ protein (E) interacts with the membrane protein to form the viral envelope
Envelope (E)
The ___________ protein is the central organiser of CoV assembly. It determines the shape of the viral envelope.
Membrane (M)
While the percentage of deaths caused by SARS CoV2 in people under 49 is low, the rate increases to 8.87% in people over __ and 24.68% in people over __.
70, 80
SARS CoV2 virus has spike proteins that attach to ____ receptors, which promotes fusion and viral uptake
ACE2
After fusion and viral uptake into the host cell, the genome is released into the cytoplasm and is immediately translated, particularly the two open reading frames ____ and ____. These generate lots of non-structural proteins. They are mechanistically required to process the life cycle and to assist with immune invasion
ORF1a and ORF1b
Most important steps of the SARS CoV2 life cycle:
S-protein: ACE2 interaction –> viral _____ and uptake –> viral replication and transcription –> viral assembly –> viral release (exocytosis)
fusion
The reading frame ____ translates into polyprotein pp1a, which leads to the production of non-structural proteins (nsp) 1-11.
ORF1a
The reading frame _____ translates into polyprotein pp1b, which leads to the production of non-structural proteins (nsp) 12-16.
ORF1b
Examples of viral __________ proteins include the envelope (E), membrane (M), and Nucleocapsid protein (N)
structural
SARS Cov2 has three important non-structural proteins: ____, Nsp15, and Nsp16, which are involved in viral host immune evasion.
Nsp1
** Nsp1- disrupts/inhibits the __________ of host proteins
translation
** Nsp15- is thought to interfere with the host ______ response. Disrupts the ability to sense viral RNA (may therefore function as an interferon antagonist)
innate
** ____- Hides the viral encoded mRNA and mimics it to make it look like a normal cell mRNA, protecting it from the host immune system
Nsp16
The function of this structural viral protein is that it is a viroporin cation selective channel
Envelope (E) protein
This protein binds host ACE2, aids in viral entry and fusion
S1/S2 “spike” protein
** Which conformation of the S1/S2 spike protein binds to host Angiotensin Converting Enzyme (ACE2) receptor?
Up or open (ONLY)
Generally speaking, the S2 site on the spike protein is the site of viral _______
fusion
Viral fusion allows the virus to enter the cell. This can only happen when the S1/S2 boundary is cleaved by host-encoded _____ protease
furin
Two cuts by proteolytic enzymes (furin protease and TMPRESS2) are required to allow full viral ______
fusion
** The S1/S2 region of the spike protein must be in the __ conformation in order to bind to ACE2 receptors
UP
The bit within the spike protein that mediates contact with ACE2 is called the receptor binding __________
motif (RBM)
The spike protein displays interesting conformational dynamics that expose and sequester the ____
RBD
Many viruses utilise the attachment of ________ in order to camouflage critical sites from the host immune system
glycans
Glycan shielding hides/camoflouges antigenic groups from the host immune system, improving the viral fitness. The ____________ allows the virus to perform immune evasion
glycosylation
The glycan structure in the RBD region hides the RBM while in the __________ /______ conformation.
closed/down
When we look at the _____ conformation of the S1/S2 spike protein glycan shield, you can see the RBM is now very much exposed, which would allow it to bind to ACE2, however the immune system could now recognise it which is bad for the virus
So this demonstrates that conformational flexibility and also the role of the glycans in shielding key antigenic sites.
open
** Which part of the spike protein undergoes the highest degree of antigenic drift?
The hACE2-binding Sb (S1) domain, or the “head” of the spike domain. (this is the part where antibodies attach). The S2 part below that tends to remain more conserved.
Antibodies attaching to the ___ domain of the spike protein (highly variable region) applies selective pressure for genetic mutation
S1
One mutation of interest was from the alpha variant- N501Y- this resulted in a higher affinity of the spike protein for the ____ receptor. This would improve viral fitness.
ACE2
In general, SARS-CoV2 mutations:
Improve ACE2 interactions
Provide immune _______
Improve viral fitness
escape
Omicron is currently the dominant variant of concern. There has been some observation of increased immune ________ with this strain.
evasion
Previous infection hx imprints on the immune system, kind of biases it, to utilise its previous memory. The cell that could recognise the new Ag don’t respond with clonal expansion. So the immune memory is biased. It’s like it’s colour blind. There is the possibility of creating a cycle of re-infection, because it prevents the immune system from creating a robust response. This phenomenon is known as- ___________ ___________ and is particularly associated with which variant of concern?
immune imprinting, Omicron
Which non-structural viral protein inhibits viral RNA sensing by the innate immune cells?
NSP15
** Which non-structural viral protein inhibits viral RNA sensing by the innate immune cells?
NSP15
** Which non-structural viral protein inhibits Type 1 IFN (cytokine expressed by cells of the innate immune system?)
NSP1
Mannose binding lectin (MBL) is a type of soluble ___ that plays an important role in innate immunity. MBL should normally bind to the spike protein. Binding is resistant in current variants, however. Reduced MBL expression d/t genetic variation in the MBL2 locus is associated with more severe dz outcome.
PRR
The immune response overview to viral infection: Ag presentation Activation of CD4+ cells Activation of CD8+ cells Stimulation of B cells Clonal expansion \_\_\_\_\_\_\_\_ generation Memory!
antibody
Neutralizing antibodies target the _________ of the spike protein
Receptor binding domain (RBD)
Measurements indicate that Abs targeting specifically the ACE2 interacting surface of the RBM have an overall ______ neutralisation activity than expected
lower
Antibody binding of RBD (technically to the side of the RBD rather than immediately on it) blocks the ____ interaction
ACE2
Reasons to get vaccinated: __________ natural and vaccinated immunity appears to offer considerable protection and SARS CoV2 infection can cause severe disease
Combined
Coronaviruses can utilise _______ __________ to mask antigenic sites. This is evident in the spike protein especially when combined with conformational flexibility (open and closed).
glycan shielding
viral mutations must strike a balance between fitness (immune ______) and consensus regions.
escape
__________, through a variety of unique mutations, has become the most successful lineage of SARS CoV2
Omicron
The innate immune system is vulnerable to coronavirus countermeasures (Nsp1 and Nsp15) yet can fight back with ________.
MBL (Mannose binding lectins)
Ab generation is focused on the ___ domain and neutralising Abs are targeted to the RBD.
S1
The RBM ACE2 interface is ______ and generally unavailable to Abs
flexible
Naturally acquired immunity is robust, but _______ acquired immunity protects from severe outcomes
vaccine
