SARS-CoV-2 Flashcards
What are some historical events in the timeline of Coronaviruses?
1931 = first coronavirus discovered
1966 = discovery of HCoV-229E
1967 = discovery of HCoV-OC43
1986 = polyprotein processing
1987 = full genome sequenced
1992 = targeted recombination
2000 = reverse genetics
2002 = SARS-CoV PANDEMIC + EM of memb. vesicle
2004 = discovery of HCoV-NL63
2005 = discovery of HCoV-HKU1
2012 = MERS-CoV PANDEMIC
2019 = SARS-CoV-2 PANDEMIC
What is the Coronavirus family?
SARS-CoV-2
= virus that causes covid-19
= belongs to the coronaviridae family
Compare MERS, SARS, Covid-19
MERS
= 2521 cases
= 866 total deaths (infections still occurring)
= 35% case fatality rate
SARS (SARS-CoV-1)
= 80098 cases
= 774 total deaths (epidemic ended)
= ~1% case fatality
= spillover reservoir unknown: civet cats
(cull to break the chain)
= most transmission occurred in hospital setting (hubs)
= no transmission until 24-36h after symptoms, lack of asymptomatic cases
(contract tracing effective)
Covid-19 (SARS-CoV-2)
= spillover reservoir unknown
= widespread community transmission
= possible abundant asymptomatic / mild cases
What is the role of bats + intermediate hosts?
= >500 CoVs been identified in bats in china
(undiscovered could reach >5000)
Describe the SARS-CoV-2 genome?
Genome
= single-stranded
= non-segmented
= positive sense
= ~30kb long genome
Encodes for 27 genes which are either:
Structural
= constitute the virion
= include S,E,M,N
Non-structural
= not structural components of virion
= include NSP1, NSP2, NSP3, NSP14 etc.
Accessory proteins
= produced only in infected cells
= includes ORF3b, ORF6, ORF7a etc.
What kind of replication occurs?
= discontinuous replication
= undergo discontinuous transcription
= leading to high recombination rates
= error rate for RNA replication is reduced by proof reading enzyme ExoN (NSP14)
(RNA photocopying)
= this is a basis for diagnostics
What is the structure and function of the coronavirus virion and viral proteins?
= ~125 nm diameter
= enveloped viruses
= numerous surface-projected club-like spikes
S protein (spike)
= entry of SARS-CoV-2 into cells
= host tropism
= protective immune responses (vaccines)
= virulence (severity of disease)
N protein (nucleocapsid)
= component of nucleocapsid
= virus transcription efficiency
= protective immune responses (vaccines)
M protein (membrane)
= most abundant amongst structural proteins
= assembly of virus particles
E protein (envelope)
= smallest amongst all the structural proteins
= virus assembly and release
What is the gate to entry in the cell?
= Cleavability (and receptor interaction)
= different variants enter differently
Delta variant
= binds to specific receptor protein: ACE2
= then uses spike protein to fuse with cell membrane
= TMPRSS2 involved to cleave the spike protein
= virus gains entry into cell
Omicron variant
= virus internalised into endosome
= fuses with lysosome to form endolysosome
= virus can be cleaved by cathepsin enzymes = which activate viral spike protein and facilitate fusion with endolysosomal membrane
= leads to release of viral RNA into cytoplasm + infection of host cell
(mutation - N856Y increases susceptibility of virus to cathepsin cleavage)
Mutations in the RBD of Spike protein determine:
= new variants
= transmissibility
= virulence
= vaccine escape
What is the SARS-CoV-2 replication cycle?
- Attachment
= virus attached to host cells by binding to ACE2 receptor on surface of human cells - Entry
= virus enters host cell by membrane fusion / endocytosis
= viral genome released into cytoplasm - Translation
= viral RNA is translated into viral proteins by host cell machinery - Replication
= viral RNA replicated by viral RNA-dependent RNA polymerase
= producing more copies of viral RNA - Assembly
= viral proteins and viral RNA come together to form new virus particles - Release
= new virus particles are released from the infected cell
= either by budding or lysis of host cell
EXTRA READING
= virus also manipulated host cell’s immune system to evade detection and destruction
= replication cycle can take several hours
= infected cells can release thousands of new virus particles = spread of COVID-19
What is the innate immunity against SARS-CoV-2?
Omicron
= upper respiratory
= less pathogenic
= BUT spread more
Delta
= deep in the lung cavity
= spread less but more pathogenic
Cytokine Storm
1. coronavirus infectes lung cells
- immune cells, including macrophages, identify the virus and produce cytokines
- cytokines attract more immune cells (e.g. WBCs) which then produce more cytokines
(cycle of inflammation - damages the lungs) - damage can occur through formation of fibrin
- weakened blood vessels allow fluid to seep in and fill lung cavities = leading to respiratory failure
(Dexamathasone = steroid, reduces cytokine storm, calms immune system without damaging cells)
EXTRA READING
= also physical barriers, PRRs, NK cells, phagocytic cells, interferons, complement system
What adaptive immunity aspects are involved in long-term protection against SARS-CoV-2?
Antibodies (from B cells):
= important in almost all currently licensed human COVID vaccines
= most recovered COVID patients have antibodies within 1-3 wks
= severe disease correlates with higher levels of antibodies
CD4+ T helper cells:
= critical for antibody responses
= protection independent on antibodies in SARS
= cross reactive immunity against pan-coronaviruses
CD8+ T killer cells:
= important in many viral infections
= may prevent re-infection
What anatomy is involved in adaptive immunity against SARS-CoV-2?
= mostly immunity (antibodies) measured in blood
= local sites of infection / portals of entry are important
= local immunity in lungs, nasal passages, oral cavity and salivary glands can consist of:
- CD8+ T cells
- CD4+ T cells
- IgG antibodies
- IgA antibodies
What mechanisms of protective immunity against covid-19 are there?
Simplest vaccine
= high level, long lasting + neutralising antibodies
= substantial protective contributions of T cell immunity against COVID-19
= hospitalisation correlate with the decent combination of antibodies, CD4 and CD8 T cells
What is the transmission of SARS-CoV-2?
Droplets
Aerosols
Smear Infection
What are some measures to control transmission of SARS-CoV-2?
= masks
(N95 - better for aerosols)
(surgical - better for droplet)
(cotton - not really useful)
= due to filtration of different particle sizes
(distance of seperation required discovered using experiments with donor, indirect recipient and controlled airflow)
